Tissue Inhibitor of Metalloproteinases: A family of secreted protease inhibitory proteins that regulates the activity of SECRETED MATRIX METALLOENDOPEPTIDASES. They play an important role in modulating the proteolysis of EXTRACELLULAR MATRIX, most notably during tissue remodeling and inflammatory processes.Tissue Inhibitor of Metalloproteinase-1: A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a N-glycosylated protein, molecular weight 28 kD, produced by a vast range of cell types and found in a variety of tissues and body fluids. It has been shown to suppress metastasis and inhibit tumor invasion in vitro.Tissue Inhibitor of Metalloproteinase-2: A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a 21-kDa nonglycosylated protein found in tissue fluid and is secreted as a complex with progelatinase A by human fibroblast and uncomplexed from alveolar macrophages. An overexpression of TIMP-2 has been shown to inhibit invasive and metastatic activity of tumor cells and decrease tumor growth in vivo.Matrix Metalloproteinases: A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.Tissue Inhibitor of Metalloproteinase-3: A member of the family of tissue inhibitor of metalloproteinases. Mutations of the gene for TIMP3 PROTEIN causes Sorsby fundus dystrophy.Matrix Metalloproteinase 2: A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Matrix Metalloproteinase 9: An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.Matrix Metalloproteinase 3: An extracellular endopeptidase of vertebrate tissues similar to MATRIX METALLOPROTEINASE 1. It digests PROTEOGLYCAN; FIBRONECTIN; COLLAGEN types III, IV, V, and IX, and activates procollagenase. (Enzyme Nomenclature, 1992)Matrix Metalloproteinase Inhibitors: Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-.Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.Matrix Metalloproteinase 1: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving FIBRILLAR COLLAGEN. It can degrade interstitial collagens, types I, II and III.Matrix Metalloproteinases, Membrane-Associated: Matrix metalloproteinases that are associated with the CELL MEMBRANE, either through transmembrane domains or GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS. Membrane-type matrix metalloproteinases may act within the pericellular environment to influence the process of CELL MIGRATION.Metalloproteases: Proteases which use a metal, normally ZINC, in the catalytic mechanism. This group of enzymes is inactivated by metal CHELATORS.Matrix Metalloproteinases, Secreted: A subclass of matrix metalloproteinases that are secreted into the pericellular space.Matrix Metalloproteinase 7: The smallest member of the MATRIX METALLOPROTEINASES. It plays a role in tumor progression.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Matrix Metalloproteinase 8: A member of the MATRIX METALLOPROTEINASES that cleaves triple-helical COLLAGEN types I, II, and III.Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.Matrix Metalloproteinase 13: A secreted matrix metalloproteinase that plays a physiological role in the degradation of extracellular matrix found in skeletal tissues. It is synthesized as an inactive precursor that is activated by the proteolytic cleavage of its N-terminal propeptide.Microbial Collagenase: A metalloproteinase which degrades helical regions of native collagen to small fragments. Preferred cleavage is -Gly in the sequence -Pro-Xaa-Gly-Pro-. Six forms (or 2 classes) have been isolated from Clostridium histolyticum that are immunologically cross-reactive but possess different sequences and different specificities. Other variants have been isolated from Bacillus cereus, Empedobacter collagenolyticum, Pseudomonas marinoglutinosa, and species of Vibrio and Streptomyces. EC 126.96.36.199.Matrix Metalloproteinase 10: A secreted matrix metalloproteinase that may play a role in matrix degradation during WOUND HEALING. It is expressed at high levels by KERATINOCYTES, suggesting its role in keratinocyte migration.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Matrix Metalloproteinase 14: A transmembrane domain-containing matrix metalloproteinase. It is synthesized as an inactive zymogen that is activated by the action of PROPROTEIN CONVERTASES such as FURIN. Matrix metalloproteinase 14 plays a direct role in the cleavage of proteins in the pericellular environment. In addition, it can function indirectly by enzymatically activating the proprotein form of MATRIX METALLOPROTEINASE 15.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Matrix Metalloproteinase 12: A secreted matrix metalloproteinase which is highly expressed by MACROPHAGES where it may play a role in INFLAMMATION and WOUND HEALING.ADAM Proteins: A family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Phenylmercuric Acetate: A phenyl mercury compound used mainly as a fungicide. Has also been used as a herbicide, slimicide, and bacteriocide.Gelatin: A product formed from skin, white connective tissue, or bone COLLAGEN. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Matrix Metalloproteinase 15: A transmembrane domain-containing matrix metalloproteinase that plays a role in the cleavage of proteins in the pericellular environment. It is synthesized as an inactive zymogen that is activated by the action of ENDOPEPTIDASES such as MATRIX METALLOPROTEINASE 14.Matrix Metalloproteinase 11: A secreted matrix metalloproteinase that is believed to play a role in EXTRACELLULAR MATRIX remodeling and cell fate determination during normal and pathological processes. Matrix metalloproteinase 11 was originally isolated in primary BREAST NEOPLASMS and may be involved in the process of tumorigenesis.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Matrix Metalloproteinase 16: A transmembrane domain-containing matrix metalloproteinase. It is synthesized as an inactive zymogen that is activated by the proteolytic action of PROPROTEIN CONVERTASES. Matrix metalloproteinase 16 plays a direct role in the cleavage of proteins in the pericellular environment. In addition, it can function indirectly by enzymatically activating the proprotein form of other MATRIX METALLOPROTEINASES such as the zymogen of MATRIX METALLOPROTEINASE 2.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Culture Media, Conditioned: Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Collagen Type I: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Procollagen N-Endopeptidase: An extracellular endopeptidase which excises a block of peptides at the amino terminal, nonhelical region of the procollagen molecule with the formation of collagen. Absence or deficiency of the enzyme causes accumulation of procollagen which results in the inherited connective tissue disorder--dermatosparaxis. EC 188.8.131.52.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes SYNOVIAL FLUID.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Ventricular Remodeling: The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle.Dipeptides: Peptides composed of two amino acid units.Aggrecans: Large HYALURONAN-containing proteoglycans found in articular cartilage (CARTILAGE, ARTICULAR). They form into aggregates that provide tissues with the capacity to resist high compressive and tensile forces.Antigens, CD147: A widely distributed cell surface transmembrane glycoprotein that stimulates the synthesis of MATRIX METALLOPROTEINASES. It is found at high levels on the surface of malignant NEOPLASMS and may play a role as a mediator of malignant cell behavior.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cartilage, Articular: A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Mice, Inbred C57BLTolloid-Like Metalloproteinases: A family of metalloproteases that are related to the DROSOPHILA protein tolloid, which is a gene product necessary for dorsal-ventral patterning in early Drosophila embryogenesis. Many members of the group may play a significant role in intercellular signaling.Time Factors: Elements of limited time intervals, contributing to particular results or situations.ElastinTransforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Proteoglycans: Glycoproteins which have a very high polysaccharide content.Doxycycline: A synthetic tetracycline derivative with similar antimicrobial activity.ThiophenesTumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Chondrocytes: Polymorphic cells that form cartilage.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Cell Line, Tumor: A cell line derived from cultured tumor cells.Endometrium: The mucous membrane lining of the uterine cavity that is hormonally responsive during the MENSTRUAL CYCLE and PREGNANCY. The endometrium undergoes cyclic changes that characterize MENSTRUATION. After successful FERTILIZATION, it serves to sustain the developing embryo.Collagen Type III: A fibrillar collagen consisting of three identical alpha1(III) chains that is widely distributed in many tissues containing COLLAGEN TYPE I. It is particularly abundant in BLOOD VESSELS and may play a role in tissues with elastic characteristics.Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Collagen Type IV: A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Cartilage: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Transforming Growth Factor beta1: A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Oncostatin M: A cytokine with both pro- and anti-inflammatory actions that depend upon the cellular microenvironment. Oncostatin M is a 28 kDa monomeric glycoprotein that is similar in structure to LEUKEMIA INHIBITORY FACTOR. Its name derives from the the observation that it inhibited the growth of tumor cells and augmented the growth of normal fibroblasts.Urokinase-Type Plasminogen Activator: A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES.Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.HemopexinNeoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Disintegrins: A family of polypeptides purified from snake venoms, which contain the arginine-glycine-aspartic acid (RGD) sequence. The RGD tripeptide binds to integrin receptors and thus competitively inhibits normal integrin-ligand interactions. Disintegrins thus block adhesive functions and act as platelet aggregation inhibitors.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Synovial Fluid: The clear, viscous fluid secreted by the SYNOVIAL MEMBRANE. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Basement Membrane: A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Organ Culture Techniques: A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Wound Healing: Restoration of integrity to traumatized tissue.Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.Pentosan Sulfuric Polyester: A sulfated pentosyl polysaccharide with heparin-like properties.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.Hydroxamic Acids: A class of weak acids with the general formula R-CONHOH.Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Fibrosarcoma: A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.Vascular Endothelial Growth Factor A: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.Bone Morphogenetic Protein 1: A bone morphogenetic protein family member that includes an active tolloid-like metalloproteinase domain. The metalloproteinase activity of bone morphogenetic protein 1 is specific for the removal of the C-propeptide of PROCOLLAGEN and may act as a regulator of EXTRACELLULAR MATRIX deposition. Alternative splicing of MRNA for bone morphogenetic protein 1 results in the production of several PROTEIN ISOFORMS.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Leukocyte Elastase: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 184.108.40.206.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Fibrinolysin: A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.Connective Tissue: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains.Snake Venoms: Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors.Corpus Luteum: The yellow body derived from the ruptured OVARIAN FOLLICLE after OVULATION. The process of corpus luteum formation, LUTEINIZATION, is regulated by LUTEINIZING HORMONE.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Extraembryonic Membranes: The thin layers of tissue that surround the developing embryo. There are four extra-embryonic membranes commonly found in VERTEBRATES, such as REPTILES; BIRDS; and MAMMALS. They are the YOLK SAC, the ALLANTOIS, the AMNION, and the CHORION. These membranes provide protection and means to transport nutrients and wastes.Pancreatic Elastase: A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC 220.127.116.11.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Trophoblasts: Cells lining the outside of the BLASTOCYST. After binding to the ENDOMETRIUM, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (PLACENTA).Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Prostaglandins F, Synthetic: Analogs or derivatives of prostaglandins F that do not occur naturally in the body. They do not include the product of the chemical synthesis of hormonal PGF.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Cell Adhesion: Adherence of cells to surfaces or to other cells.Crotalid Venoms: Venoms from snakes of the subfamily Crotalinae or pit vipers, found mostly in the Americas. They include the rattlesnake, cottonmouth, fer-de-lance, bushmaster, and American copperhead. Their venoms contain nontoxic proteins, cardio-, hemo-, cyto-, and neurotoxins, and many enzymes, especially phospholipases A. Many of the toxins have been characterized.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Bothrops: A genus of poisonous snakes of the VIPERIDAE family. About 50 species are known and all are found in tropical America and southern South America. Bothrops atrox is the fer-de-lance and B. jararaca is the jararaca. (Goin, Goin, and Zug, Introduction to Herpetology, 3d ed, p336)Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.Endomyocardial Fibrosis: A condition characterized by the thickening of the ventricular ENDOCARDIUM and subendocardium (MYOCARDIUM), seen mostly in children and young adults in the TROPICAL CLIMATE. The fibrous tissue extends from the apex toward and often involves the HEART VALVES causing restrictive blood flow into the respective ventricles (CARDIOMYOPATHY, RESTRICTIVE).Interleukin-1beta: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.Kinetics: The rate dynamics in chemical or physical systems.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Aorta: The main trunk of the systemic arteries.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Adenoviridae: A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.Aorta, Abdominal: The aorta from the DIAPHRAGM to the bifurcation into the right and left common iliac arteries.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Relaxin: A water-soluble polypeptide (molecular weight approximately 8,000) extractable from the corpus luteum of pregnancy. It produces relaxation of the pubic symphysis and dilation of the uterine cervix in certain animal species. Its role in the human pregnant female is uncertain. (Dorland, 28th ed)DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Inflammation Mediators: The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Crotalus: A genus of snakes of the family VIPERIDAE, one of the pit vipers, so-called from the pit hollowing out the maxillary bone, opening between the eye and the nostril. They are distinctively American serpents. Most of the 25 recognized species are found in the southwestern United States and northern Mexico. Several species are found as far north as Canada and east of the Mississippi, including southern Appalachia. They are named for the jointed rattle (Greek krotalon) at the tip of their tail. (Goin, Goin, and Zug: Introduction to Herpetology, 3d ed; Moore: Poisonous Snakes of the World, 1980, p335)Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Breast Neoplasms: Tumors or cancer of the human BREAST.Ovary: The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Molecular Weight: The sum of the weight of all the atoms in a molecule.Collagen Type II: A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.Coculture Techniques: A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Transcription Factor AP-1: A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.Blood-Brain Barrier: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.Real-Time Polymerase Chain Reaction: Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.Fibrillar Collagens: A family of structurally related collagens that form the characteristic collagen fibril bundles seen in CONNECTIVE TISSUE.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Ovulation: The discharge of an OVUM from a rupturing follicle in the OVARY.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Aortic Aneurysm, Abdominal: An abnormal balloon- or sac-like dilatation in the wall of the ABDOMINAL AORTA which gives rise to the visceral, the parietal, and the terminal (iliac) branches below the aortic hiatus at the diaphragm.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Joint Capsule: The sac enclosing a joint. It is composed of an outer fibrous articular capsule and an inner SYNOVIAL MEMBRANE.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Tissue inhibitor of metalloproteinases 2 (TIMP2) is a gene and a corresponding protein. The gene is a member of the TIMP gene ... "Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type 1- ... high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human ... "Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor ...
Balance in the MMP activity is usually achieved by tissue inhibitor of metalloproteinases (TIMP). Rather than absolute ... Vaalamo, M.; Leivo, T.; Saarialho-Kere, U. (1999). "Differential expression of tissue inhibitors of metalloproteinases (TIMP-1 ... "Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients". Diabetologia ... Increased matrix metalloproteinases (MMP) activity In order for a wound to heal, extracellular matrix not only needs to be laid ...
TIMP metallopeptidase inhibitor 1, also known as TIMP1, a tissue inhibitor of metalloproteinases, is a glycoprotein that is ... "Tissue inhibitor of metalloproteinase (TIMP)-1: the TIMPed balance of matrix metalloproteinases in the central nervous system ... Nothnick WB, Soloway P, Curry TE (May 1997). "Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during ... "Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory". The ...
Docherty, A.J.P.; Murphy, G. (1990). "The tissue metalloproteinase family and the inhibitor TIMP: a study using cDNAs and ... 1986). "A metalloproteinase from human rheumatoid synovial fibroblasts that digests connective tissue matrix components. ... Chin, J.R.; Murphy, G.; Werb, Z. (1985). "Stromelysin, a connective tissue-degrading metalloendopeptidase secreted by ... Emonard, H.; Grimaud, J.A. (1990). "Matrix metalloproteinase. A review". Cell. Mol. Biol. 36: 131-153. PMID 2165861. ...
The catalytic domain of MMP-3 can be inhibited by tissue inhibitors of metalloproteinases (TIMPs). The n-terminal fragment of ... "Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1". Nature. 389 (6646): 77-81. doi:10.1038/ ... Tissue from uninjured WT and KO mice brains was also treated with active MMP-3. Both the WT and KO tissues showed a drop in ... shown to play a functional role in substrate binding and/or in interactions with the tissue inhibitors of metalloproteinases ( ...
"The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP ... 1994). "A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene family is regulated during G1 progression, ... "Cloning of the cDNA encoding human tissue inhibitor of metalloproteinases-3 (TIMP-3) and mapping of the TIMP3 gene to ... characterization of human tissue inhibitor of metalloproteinase-3 and detection of three additional metalloproteinase inhibitor ...
MiR-712 targets tissue inhibitor of metalloproteinases 3 (TIMP3). TIMPs normally regulate activity of matrix metalloproteinases ... Expressed by endothelial cells, TIMP3 is the only ECM-bound TIMP. A decrease in TIMP3 expression results in an increase of ECM ... miRNA research revealed different sets of miRNAs expressed in different cell types and tissues and multiple roles for miRNAs in ... Let-7 accumulates in human tissues during the course of aging. When let-7 was ectopically overexpressed to mimic accelerated ...
Klenotic PA, Munier FL, Marmorstein LY, Anand-Apte B (2004). "Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding ... Giltay R, Timpl R, Kostka G (2000). "Sequence, recombinant expression and tissue localization of two novel extracellular matrix ...
"Engineering N-terminal domain of tissue inhibitor of metalloproteinase (TIMP)-3 to be a better inhibitor against tumour ... "The C-terminal domains of TACE weaken the inhibitory action of N-TIMP-3". FEBS Letters. 520 (1-3): 102-6. doi:10.1016/S0014- ... "A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells". Nature. 385 (6618): 729-33. doi:10.1038 ... "A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells". Nature. 385 (6618): 729-33. doi:10.1038 ...
Furthermore, it secretes TIMP 1 and 2, naturally occurring inhibitors of matrix metalloproteinases, which prevents them from ... This damage is characterized by the replacement of normal liver tissue by scar tissue. Typically, the disease develops slowly ... The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal parenchyma. This scar tissue ... Thickening and shortening of palmar fascia (tissue on the palm of the hands) that leads to flexion deformities of the fingers. ...
February 2006). "Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in patients with ... The low level of uric acid found in MS victims is manifestedly causative rather than a tissue damage consequence in the white ... A special role is played by Matrix metalloproteinases. These increase BBB T-cell permeability, specially in the case of MMP-9 ... "Tissue-type plasminogen activator is a regulator of monocyte diapedesis through the brain endothelial barrier". Journal of ...
"Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type 1- ... Matrix metalloproteinase-14 is an enzyme that in humans is encoded by the MMP14 gene. Proteins of the matrix metalloproteinase ... Matrix metalloproteinase ARK5 GRCh38: Ensembl release 89: ENSG00000157227 - Ensembl, May 2017 GRCm38: Ensembl release 89: ... Nagase H, Woessner JF (1999). "Matrix metalloproteinases". J. Biol. Chem. 274 (31): 21491-4. doi:10.1074/jbc.274.31.21491. PMID ...
... that control the maternal extracellular matrix and inhibition of tissue-inhibitors of matrix-metalloproteinases (TIMP). hCG ... The mix of hormones characteristic of early pregnancy promote natural growth of maternal tissues and weight gain. In the second ... Ma, W. et al (2001). Adult Tissue Angiogenesis: Evidence for negative regulation by estrogen in the uterus. Molecular ... hCG secreted by cytotrophoblastic cells of the blastocyst controls endometrial tissue remodeling by both activation of matrix ...
For risk assessment for moderate to severe AKI, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth ... Nephrocheck uses two urinary cell-cycle arrest biomarkers (e.g., TIMP-2 and IGFBP7) to determine if a person is at increased ...
... high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin-like domain of human ... "Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2 ... A complex of membrane type 1 MMP (MT1-MMP/MMP14) and tissue inhibitor of metalloproteinase 2 recruits pro-MMP 2 from the ... MMP inhibitors could also be administered along with cytotoxic agents or other proteinase inhibitors. Finally, MMP inhibitors ...
"Total conversion of tissue inhibitor of metalloproteinase (TIMP) for specific metalloproteinase targeting: fine-tuning TIMP-4 ... Huang W, Li WQ, Dehnade F, Zafarullah M (2002). "Tissue inhibitor of metalloproteinases-4 (TIMP-4) gene expression is increased ... 1997). "Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP-4) to the COOH-terminal hemopexin- ... 2003). "Identification, regulation and role of tissue inhibitor of metalloproteinases-4 (TIMP-4) in human platelets". Br. J. ...
Matrix Metalloproteinases 2) to TIMP1 (Tissue Inhibitor Metalloproteinases 1) may be responsible for the abnormal degradation ... However, other studies have also shown MMP9 involvement with no differences in TIMP expression. The size of the proximal aorta ...
... gene transfer of tissue inhibitor of metalloproteinase-1 linked to the amino terminal fragment of urokinase (TIMP-1.ATF), a ... The No-touch technique is where the vein is harvested with the surrounding tissues, keeping the vasa vasorum and the nerves in ... The damage causes local release of tissue factors and reduced bioavailability of prostacyclin and nitric oxide (NO), all of ... cell-surface directed matrix metalloproteinase inhibitor". Journal of vascular surgery. 51 (2): 429-37. doi:10.1016/j.jvs. ...
Timp or TIMP may refer to: Timp, a colloquial word for timpani Tissue inhibitor of metalloproteinases, a family of proteins ... Timp (short for Mount Timpanogos) is the second highest mountain in Utah's Wasatch Range. ... that act as enzyme inhibitors Thioinosine monophosphate, an intermediate metabolite of azathioprine Temp (disambiguation). ...
This determines substrate specificity and is the site for interaction with TIMP's (tissue inhibitor of metalloproteinases). The ... which comprise a family of four protease inhibitors: TIMP-1, TIMP-2, TIMP-3, and TIMP-4. Synthetic inhibitors generally contain ... The MMPs are inhibited by specific endogenous tissue inhibitor of metalloproteinases (TIMPs), ... Gross J, Lapiere C (1962). "COLLAGENOLYTIC ACTIVITY IN AMPHIBIAN TISSUES: A TISSUE CULTURE ASSAY". Proc Natl Acad Sci USA. 48 ( ...
The role of the pro-MMP-9/TIMP-1 complex is still unknown. Brew K, Dinakarpandian D, Nagase H (2000). "Tissue inhibitors of ... The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitors of metalloproteinases (TIMPs), which ... Tissue Inhibitor of Metalloproteinases at the US National Library of Medicine Medical Subject Headings (MeSH). ... The complex of latent MMP-2 (pro-MMP-2)with TIMP-2 serves to facilitate the activation of pro-MMP-2 at the cell surface by MT1- ...
... of the interleukin-10E1 pathway and tissue inhibitor of metalloproteinase-1 expression is enhanced by proteasome inhibitors in ... Wang M, Hu Y, Shima I, Stearns ME (2003). "IL-10/IL-10 receptor signaling regulates TIMP-1 expression in primary human prostate ... is a novel marker of hepatic stellate cells and binding partner of the protein inhibitor of activated STAT1". Biochem. J. 359 ( ...
MMP-2 is unlike other MMP's as its activity is modulated by metalloproteases called tissue inhibitor of metalloproteases (TIMP ... Matrix metalloproteinases (MMPs) MMP-2 is the main metalloprotease secreted by breast-cancer cells or induced in the adjacent ... Cancer cells can then use the proteinase to facilitate tissue invasion, which requires the degradation of connective tissue ... and natural tissue inhibitors of metalloproteases (TIMPs). Regulated proteolysis is an important mechanism to maintain ...
"Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and -4 in endometrium throughout ... 2005). "Endometrial TIMP-4 mRNA is high at midcycle and in hyperplasia, but down-regulated in malignant tumours. Coordinated ... "Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases- ... 2001). "Characterization of matrix metalloproteinase-26, a novel metalloproteinase widely expressed in cancer cells of ...
... at various levels for example by endogenous inhibitors like α2-macroglobulin and the tissue inhibitors of metalloproteinases ( ... TIMP-1 for example favors to inhibit MMP-9. Other examples are TIMP-2 and TIMP-4 which are more potent MMP-2 inhibitors than ... Protein inhibitors such as α2-macroglobulin are known to work with metalloproteinases. The first generation of MMP inhibitors ... Metalloprotease inhibitors are cellular inhibitors of the Matrix metalloproteinases (MMPs). MMPs belong to a family of zinc- ...
... as blood vessels in adipose tissue never fully mature, and are thus destroyed by angiogenesis inhibitors. Angiogenesis ... matrix metalloproteinase inhibitors. angiostatin. inhibit cell proliferation and induce apoptosis of endothelial cells. ... TIMP and CDAI. inhibit cell migration of endothelial cells. Meth-1 and Meth-2. ... Angiogenesis Inhibitors for Cancer - from The Angiogenesis Foundation, 23 June 2009. *Angiogenesis Inhibitors for Eye Disease ...
1991) Decreased tissue inhibitor of metalloproteinases (TIMP) in abdominal aortic aneurysm tissue: A preliminary report. J Surg ... Their activity is controlled by tissue inhibitors of metalloproteinases (TIMPs). Decreased TIMP-1 and TIMP-2 expression in the ... Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Polymorphisms in a Caucasian Population with Abdominal Aortic Aneurysm. ... 2003) Tissue inhibitor of metalloproteinases-1, -2, and -3 polymorphisms in a white population with intracranial aneurysms. ...
Tissue inhibitor metalloproteinase-2 (TIMP-2) and IGF-binding protein-7 (IGFBP7) have been validated for risk stratification in ... Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term ... Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term ... Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term ...
The expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) is required for normal development of zebrafish embryos.. ... steps and inhibition by endogenous inhibitors like alpha2-macroglobulin and the tissue inhibitors of metalloproteinases (TIMPs ... TIMPs are the key inhibitors in tissue. The expression of both MMPs and TIMPs is controlled during tissue remodeling to ... Additionally, TIMP-2 has been reported to have growth factor activities. To further study the function of TIMP-2 in development ...
Complex membrane type-1 matrix metalloproteinase (MT1-MMP) with tissue inhibitor of metalloproteinase-1 (TIMP-1). *DOI: 10.2210 ... A single point mutation at the distal site of the endogenous tissue inhibitor of metalloproteinase 1 (TIMP-1) enables this ... Metalloproteinase inhibitor 1. B, C. 125. Homo sapiens. Mutation(s): 3 Gene Names: TIMP1, CLGI, TIMP. ... The Intrinsic Protein Flexibility of Endogenous Protease Inhibitor TIMP-1 Controls Its Binding Interface and Affects Its ...
Predictive role of HER2/neu, topoisomerase-II-alpha, and tissue inhibitor of metalloproteinases (TIMP-1) for response to ... and TIMP-1. Tumor tissue was available in a representative cohort of 772 cases of the WSG EC-DOC Trial collective which ... Breast cancer Taxanes Topoisomerase-II-alpha TIMP-1 HER2/neu This is a preview of subscription content, log in to check access. ... Munro A, Bartels A, Balslev E et al (2013) Is TIMP-1 immunoreactivity alone or in combination with other markers a predictor of ...
Involvement of a region near valine-69 of tissue inhibitor of metalloproteinases (TIMP)-1 in the interaction with matrix ... Involvement of a region near valine-69 of tissue inhibitor of metalloproteinases (TIMP)-1 in the interaction with matrix ... Involvement of a region near valine-69 of tissue inhibitor of metalloproteinases (TIMP)-1 in the interaction with matrix ... Involvement of a region near valine-69 of tissue inhibitor of metalloproteinases (TIMP)-1 in the interaction with matrix ...
Transcriptional activity of the human tissue inhibitor of metalloproteinases 1 (TIMP-1) gene in fibroblasts involves elements ... Transcriptional activity of the human tissue inhibitor of metalloproteinases 1 (TIMP-1) gene in fibroblasts involves elements ... Transcriptional activity of the human tissue inhibitor of metalloproteinases 1 (TIMP-1) gene in fibroblasts involves elements ... Transcriptional activity of the human tissue inhibitor of metalloproteinases 1 (TIMP-1) gene in fibroblasts involves elements ...
Tissue Inhibitor of Metalloproteinase-3) Antibody - Without BSA, Rabbit Polyclonal Antibody validated in IHC-P, IF, FC (AH10767 ... AH12415: TIMP-3 (Tissue Inhibitor of Metalloproteinase-3) Antibody. AH10766: TIMP-3 (Tissue Inhibitor of Metalloproteinase-3) ... Tissue Inhibitor of Metalloproteinase-3) Antibody - Without BSA TIMP-3 (Tissue Inhibitor of Metalloproteinase-3) Antibody - ... Metalloproteinase inhibitor 3, Protein MIG-5, Tissue inhibitor of metalloproteinases 3, TIMP-3, TIMP3. ...
Tissue inhibitor of metalloproteinases 1 TIMP-1, TIMP1, CLGI, TIMP) TIMP-1 (Tissue inhibitor of metalloproteinases, EPA , TAK, ... Collagenase inhibitor, Tissue inhibitor of metalloproteinases 1 TIMP-1, TIMP1, CLGI, TIMP). This gene belongs to the TIMP gene ... Tissue inhibitor of metalloproteinases, EPA , TAK, Metalloproteinase Inhibitor 1, Erythroid-potentiating activity, Fibroblast ... Metalloproteinase Inhibitor 1, Erythroid-potentiating activity, Fibroblast collagenase inhibitor, ...
TIMP)-2 forms a noncovalent complex with the precursor of matrix metalloproteinase 2 (proMMP-2, progelatinase A) through ... formed a new complex with TIMP-2 by binding to the N-terminal inhibitory domain of the inhibitor without processing the ... it bound to TIMP-2 and rendered proMMP-2 readily activatable by APMA. These results indicate that the blockage of TIMP-2 of the ... Thus the APMA-treated proMMP-2*-TIMP-2 complex exhibited no gelatinolytic activity. In the presence of a small amount of free ...
TIMP-3 is one of the four known TIMPs (TIMP-1, TIMP-2, TIMP-3 and TIMP-4). It is known to be tightly bound to the matrix ... Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and ... The micrographs show tissue inhibitor of metalloproteinases (TIMP)-3 in the cytoplasm of a lobular carcinoma (a), both the ... Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: Relation to tumor ...
... steps and inhibition by endogenous inhibitors like alpha2-macroglobulin and the tissue inhibitors of metalloproteinases (TIMPs ... TIMPs are the key inhibitors in tissue. The expression of both MMPs and TIMPs is controlled during tissue remodeling to ... Additionally, TIMP-2 has been reported to have growth factor activities. To further study the function of TIMP-2 in development ... We have successfully isolated a TIMP-2 homologue from zebrafish (zTIMP-2). This zebrafish TIMP-2 showed high similarity to ...
Matrix metalloproteinases (MMP-2 and 9) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and 2) during the course of ... Balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in the cervical mucus plug ... EVIDENCE FOR THE TISSUE INHIBITOR OF METALLOPROTEINASES-1 (TIMP-1) IN HUMAN POLYMORPHONUCLEAR LEUKOCYTES. TRIEBEL S, BLASER J, ... A tissue inhibitor of metalloproteinases (TIMP)-1 was isolated from human polymorphonuclear leukocytes (PMNL) in a complex with ...
metalloproteinase-2;. MT MMP,. membrane-type metalloproteinase;. PGE2,. prostaglandin E2;. TIMP,. tissue inhibitors of ... The MMP-2 and tissue inhibitors of metalloproteinases (TIMP) antibodies were rabbit polyclonal anti-human MMP-2 and TIMP ( ... and inhibition of activity by tissue inhibitors of metalloproteinases (TIMP) (33). We investigated the expression levels of ... TIMP-1 and TIMP-2 in our cell lines by Western blot analysis and found no significant expression of TIMP-1 or TIMP-2 in either ...
TIMP. tissue inhibitor of metalloproteinases. Enzymes. Matrix metalloproteinases (EC 3.4.24.-). vertebrate collagenase (EC 3.4. ... Grant, G. A., Goldberg, G. I., Wihelm, S. M., He, C. & Eisen, A. Z. (1992) in Matrix metalloproteinases and inhibitors ( ... Murphy, G., Ward, R., Gavrilovic, J. & Atkinson, S. (1992) in Matrix metalloproteinases and inhibitors (Birkedal-Hansen, H., ed ... Nagase, H., Suzuki, K., Morodomi, T., Enghild, J. J. & Salvesen, G. (1992) in Matrix metalloproteinases and inhibitors ( ...
... tissue inhibitor of metalloproteinases)",. abstract = "To define domains of tissue inhibitor of metalloproteinases (TIMP-1) ... Functional domains of human TIMP-1 (tissue inhibitor of metalloproteinases). Journal of Biological Chemistry. 1994 Jul 22;269( ... Functional domains of human TIMP-1 (tissue inhibitor of metalloproteinases). In: Journal of Biological Chemistry. 1994 ; Vol. ... Functional domains of human TIMP-1 (tissue inhibitor of metalloproteinases). M. Kirby Bodden, Gregory J. Harber, Bente Birkedal ...
TIMP-2,. tissue inhibitor of metalloproteinase 2;. bFGF,. basic fibroblast growth factor;. I.U.,. infectious units;. GFP,. ... Matrix Metalloproteinase-9 Is Required for Adequate Angiogenic Revascularization of Ischemic Tissues: Potential Role in ... surface of invasive cells by a multimeric receptor/activation complex consisting of the tissue inhibitor of metalloproteinase 2 ... a TIMP-2/MT1-MMP receptor complex and a TIMP-2-free MT1-MMP processing enzyme that initiates MMP-2 activation by cleaving the N ...
Tissue inhibitor of metalloproteinases 1 (TIMP-1) is a protein with proteinase-inhibiting and cytokine properties which has ... E. Oelmann, H. Herbst, M. Zühlsdorf et al., "Tissue inhibitor of metalloproteinases 1 is an autocrine and paracrine survival ... In fact, in situ hybridization showed TIMP-1 RNA expression on HRSC, while TIMP-1 production by HRSC cells was demonstrated on ... B. A. Bladergroen, C. J. L. M. Meijer, R. L. Ten Berge et al., "Expression of the granzyme B inhibitor, protease inhibitor 9, ...
Tissue Inhibitor of Metalloproteinases. Tissue Inhibitor of Metalloproteinase-1. Matrix Metalloproteinase Inhibitors. Tissue ... This study will examine the effect of Pioglitazone on tissue inhibitor of metalloproteinases (TIMP-3) and on TNF-alfa ... The investigators propose that Tissue Inhibitor of MetalloProteinase-3 (TIMP-3) and TNF-alfa converting enzyme (TACE) play a ... Effect of Pioglitazone on Tissue Inhibitor of Metalloproteinases 3 (TIMP-3) and TNF (Tumor Necrosis Factor)-α Converting Enzyme ...
... and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1: ... TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS ( ... are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of ... N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for ...
... ... IL-6, however, is identified as a potent inducer of de novo synthesis of tissue inhibitor of metalloproteinases-1/erythroid ... Effects of different preparations of IL-6 on production of collagenase and tissue inhibitor of metalloproteinases-1/erythroid ... These results define new biological activities of IL-6 and provide further insight into the regulation of connective tissues by ...
Tissue Inhibitor of Metalloproteinase-3); Rabbit Polyclonal (Concentrate) - RA0309-C.1 ( Antibodies, Research Antibodies) ... TIMP-3 (Tissue Inhibitor of Metalloproteinase-3); Rabbit Polyclonal (Concentrate). Species: Rabbit. Immunogen: Recombinant ...
TIMP:. tissue inhibitors of metalloproteinase. ROS:. Reactive oxygen species. Lv-shNfe2l2:. Lentivirus-based vector with shRNA ... However, childbirth injury induced varying degrees of damage to connective tissues, muscle tissues, and nerve tissues that may ... MMPs are zinc-dependent proteases that play important roles in ECM degradation in many tissues. TIMPs are the inhibitor of MMPs ... In addition, connective tissues and muscular tissues enable the vaginal wall to have enough strength and toughness to maintain ...
TIMP-3 variants appear to contribute to susceptibility to PBD. This may be through the inflammatory reaction rather than the ... Promoter variants in tissue inhibitor of metalloproteinase-3 (TIMP-3) protect against susceptibility in pigeon breeders ... Promoter variants in tissue inhibitor of metalloproteinase-3 (TIMP-3) protect against susceptibility in pigeon breeders ... Background: Tissue inhibitors of metalloproteinases (TIMPs) play a major role in extracellular matrix turnover in the lung. ...
1993) Tissue inhibitor of metalloproteinases (TIMP, aka EPA)structure, control of expression and biological functions. ... Using a double transgenic murine hepatic tumor model, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP-1) ... 1997) Inhibition of angiogenesis by tissue inhibitor of metalloproteinase-3. Invest. Opthalmol. Vis. Sci. 38:817-823. ... Inhibition of tumor growth and metastasis of human breast cancer cells transfected with tissue inhibitor of metalloproteinase-4 ...
TIMPsInhibitionProteinEnzymesDegradationProteinsAntibodyConnective tissuesBalance between matrix metalloproteinasesInhibitInhibitsExpressionCollagenPrecursorTIMP1ReceptorAngiogenesisPlasminogen ActivatorSecreteMurineMolecularMetastasisImbalanceEndogenous inhibitorMetalloendopeptidase inhibitor activityProteolyticInhibitoryMMP2GelatinaseActivityMembraneNecrosis factorRecombinant humanDegradeGenesSelectiveGene familyPhosphodiesterase inhibitorLevelsLiverInflammationFunctionalStructuralTIMP2
- Their activity is controlled by tissue inhibitors of metalloproteinases (TIMPs). (springer.com)
- MMP activities are controlled by a combination of proteolytic pro-enzyme activation steps and inhibition by endogenous inhibitors like alpha2-macroglobulin and the tissue inhibitors of metalloproteinases (TIMPs). (nih.gov)
- TIMPs are the key inhibitors in tissue. (nih.gov)
- The expression of both MMPs and TIMPs is controlled during tissue remodeling to maintain a balance in the turnover of extracellular matrix. (nih.gov)
- Tissue inhibitors of metalloproteinases (TIMPs) inhibit matrix metalloproteinases (MMPs) by forming a 1:1 stoichiometric complex, but the inhibition mechanism of these inhibitors is not known. (biochemj.org)
- The active forms of all of the matrix metalloproteinases (MMPs) are inhibited by a family of specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). (biochemj.org)
- The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. (ox.ac.uk)
- The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. (ox.ac.uk)
- Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. (ox.ac.uk)
- The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. (ox.ac.uk)
- Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases. (ox.ac.uk)
- Tissue inhibitors of metalloproteinases (TIMPs) play a major role in extracellular matrix turnover in the lung. (cdc.gov)
- The structural and functional integrity of the ECM is ensured through a balance between matrix metalloproteinases (MMPs), which cleave ECM proteins, and their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs) ( 37 ). (physiology.org)
- Unique among the TIMPs, TIMP-3 inhibits a wide range of MMPs, displays high cardiac expression, and is sequestered to the ECM ( 38 ). (physiology.org)
- As it is ECM bound, TIMP-3 may have more influential biological effects compared with the other TIMPs that are soluble and able to diffuse away from the interaction site. (physiology.org)
- Introduction: In bile duct injuries (BDI), cholestasis and cholangitis can alter the fibrinolytic system by promoting an increase of extracellular matrix depositions which favor an imbalance between metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). (scirp.org)
- In this review, we examine the impact of changes in acetylation on the expression of the MMPs and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs). (biologicalworld.com)
- Tissue inhibitors of metalloproteinases (TIMPs) regulate the ECM turnover through negative regulation of matrix metalloproteinases (MMPs), which degrade the ECM structural proteins. (ahajournals.org)
- Tissue inhibitor of metalloproteinases 2 is unique among TIMPs in activating pro-MMP2 in addition to inhibiting a number of MMPs. (ahajournals.org)
- 3 - 7 Matrix metalloproteinases (MMPs) degrade ECM proteins, whereas their proteolytic activity is kept in check by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). (ahajournals.org)
- Fibrosis is characterized by high levels of extracellular matrix (ECM, non-functional connective tissue) components extremely rich in collagen type I. The matrix metalloproteinases (MMPs, matrix degradation enzymes), and the tissue inhibitor of metalloproteinases (TIMPs) play a crucial role in the fine regulation of ECM turnover, which is altered in most pathological states associated with liver fibrosis [ 8 ]. (intechopen.com)
- The proteolytic activity of MMPs may be inhibited by naturally occurring inhibitors, the TIMPs. (aacrjournals.org)
- Metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are involved in several key pathways of tumor growth, invasion and metastasis, but little is known about their expression according to different molecular subtypes of breast cancer. (biomedcentral.com)
- To determine: (i) whether PSCs secrete matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and, if so (ii) whether MMP and TIMP secretion by PSCs is altered in response to known PSC activating factors such as tumour necrosis factor α (TNF-α), transforming growth factor β1 (TGF-β1), interleukin 6 (IL-6), ethanol, and acetaldehyde. (bmj.com)
- The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitors of metalloproteinases (TIMPs), which comprise a family of four protease inhibitors: TIMP1, TIMP2, TIMP3 and TIMP4. (wikipedia.org)
- For example, TIMP-1 inhibits MMP-7, MMP-9, MMP-1 and MMP-3 better than TIMP-2, and TIMP-2 inhibits MMP-2 more effectively than other TIMPs. (wikipedia.org)
- Several long peptides (n = 20-34), together covering three-fourths of the human TIMP-1 sequence, were able to block inhibition of human FIB-CL by TIMP-1. (elsevier.com)
- Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. (ox.ac.uk)
- The purified protein showed metalloproteinase-inhibitory activity in two independent assays: reverse zymography and inhibition of collagenase activity. (uni-bielefeld.de)
- The effects of TIMP-3 are mediated via inhibition of EGFR expression/phosphorylation, and decreases in JNK and SP-1 signaling. (physiology.org)
- Ac-SDKP is cleared by the N domain of ACE and its plasma and tissue levels therefore significantly increase following ACE inhibition ( 3 , 15 ). (spandidos-publications.com)
- The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. (scielo.br)
- The results indicated that neutralisation of both IL-1 and TNF-α was needed to achieve a degree of cytokine (IL-6, IL-8, and monocyte chemoattractant protein-1) and matrix metalloproteinase (1, 3, 9, and 13) inhibition, as assessed by enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction (RT-PCR), similar to that observed in CD14 + -depleted cultures. (biomedcentral.com)
- Inhibition of ICAM-1 by antibody or siRNA approaches reversed the anti-invasive and TIMP-1-upregulating action of CBD and the likewise ICAM-1-inducing cannabinoids Δ(9)-tetrahydrocannabinol and R(+)-methanandamide when compared to isotype or nonsilencing siRNA controls. (nih.gov)
- Activation of MAPK pathways is regarded the consequence of irradiation-induced DNA damage, thus their inhibition can counteract the radiosenzitizing effect of the PARP inhibitor. (jove.com)
- Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with. (nih.gov)
- Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with AKI. (nih.gov)
- Tissue inhibitor metalloproteinase-2 (TIMP-2) and IGF-binding protein-7 (IGFBP7) have been validated for risk stratification in AKI. (nih.gov)
- In addition, at the protein level, immunoreactive zTIMP-2 was detected using antibody against recombinant human TIMP-2. (nih.gov)
- A single point mutation at the distal site of the endogenous tissue inhibitor of metalloproteinase 1 (TIMP-1) enables this clinical target protein to tightly bind and inhibit membrane type 1 matrix metalloproteinase (MT1-MMP) by increasing only the association constant. (rcsb.org)
- This work quantifies the effect of a single point mutation on the protein conformational dynamics and function of TIMP-1. (rcsb.org)
- Here we argue that controlling the intrinsic protein dynamics of MMP endogenous inhibitors may be utilized for rationalizing the design of selective novel protein inhibitors for this class of enzymes. (rcsb.org)
- 50 years old and normal chromosome 17 status, high TIMP-1 and low topoisomerase-II-alpha protein expression. (springer.com)
- Our aim was to study the expression pattern of tissue inhibitor of metalloproteinases (TIMP)-3 protein in invasive breast carcinoma, and its clinicopathological and prognostic value as well as its relation to markers indicative of the tumor phenotype. (biomedcentral.com)
- TIMP-3 protein was immunodetected in the cytoplasm of the malignant cells and the peritumoral stroma, as well as in in situ carcinoma and normal epithelium. (biomedcentral.com)
- Reduced expression of TIMP-3 protein within cancer cells was correlated with carcinomas of high nuclear and histological grade ( p = 0.032 and p = 0.015, respectively), and low ER expression ( p = 0.053). (biomedcentral.com)
- Reduced expression of TIMP-3 protein within cancer cells was found to have an unfavorable impact on disease-free survival ( p = 0.052) in the entirety of the patient population, as well as in both subgroups of lymph-node-positive and mutant-p53-negative patients ( p = 0.007 and p = 0.037, respectively). (biomedcentral.com)
- Stromal localization of TIMP-3 protein was found to have no clinicopathological or prognostic value. (biomedcentral.com)
- This is the first immunohistochemical study to show that TIMP-3 protein within cancer cells is associated with tumor phenotype. (biomedcentral.com)
- Reduced expression of TIMP-3 protein within cancer cells was found to correlate with an aggressive tumor phenotype, negatively affecting the disease-free survival of both subgroups of lymph node-positive and mutant-p53-negative patients. (biomedcentral.com)
- However, the direct or indirect effects of astrocyte HIV-1 protein expression on TIMP-1 regulation are not well studied. (unt.edu)
- Concurrently, time-dependent changes in TIMP-1 and CCL2 mRNA and protein levels were measured as indicators of astrocyte activation. (unt.edu)
- Since C/EBPβ is a known TIMP-1 regulator, alterations in C/EBPβ mRNA and protein levels were analyzed. (unt.edu)
- We propose that TIMP-1 is differentially regulated by HIV-1 protein expression in astrocytes, which mimic viral CNS reservoirs, and may have implications in HAND neuropathogenesis. (unt.edu)
- TIMP-1 inhibits apoptosis in breast carcinoma cells via a pathway involving pertussis toxin-sensitive G protein and c-Src. (uni-bielefeld.de)
- Ligand blotting showed that IGFBP-3 protein levels were increased in TIMP-1-overexpressing double transgenic littermates, whereas IGFBP-3 mRNA levels were not different, suggesting that TIMP-1 affects IGFBP-3 at a posttranscriptional level. (rupress.org)
- As a consequence of reduced IGFBP-3 proteolysis and elevated IGFBP-3 protein levels, dissociable IGF-II levels were significantly lower in TIMP-1-overexpressing animals. (rupress.org)
- JNK phosphorylation and EGFR protein levels were increased in TIMP-3 −/− cardiomyocytes and heart tissues. (physiology.org)
- Hypersensitive C-reaction protein, homocysteine, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, vascular endothelial growth factor and neopterin levels were significantly higher in CAE and coronary artery disease (CAD) patients than in controls without CAE. (scielo.br)
- TIMP3 (TIMP Metallopeptidase Inhibitor 3) is a Protein Coding gene. (genecards.org)
- In the postnatal state, new blood vessels routinely traverse a dense connective tissue matrix largely comprised of type I collagen, the major extracellular protein found in mammals ( Hay, 1991 ). (rupress.org)
- Various kinase inhibitors, especially inhibitors of cell cyclin-dependent kinase (rescovitine), rho and Ca2+-dependent protein kinase (Y-27632), tyrosine kinase (tyrphostin AG879), phosphatidylinositol 3-kinase (bisindolylmaleimide I, BIM I), and Ca2+/calmodulin kinase (chelerythrine), strongly inhibited collagen gel contraction. (omicsonline.org)
- As a consequence of this tissue turnover, there is a release of several protein degradation fragments specific for the combination of the involved proteases, the affected organ and the disease. (biomedcentral.com)
- In athymic nude mice, CBD elicited a 2.6- and 3.0-fold increase of ICAM-1 and TIMP-1 protein in A549 xenografts, as compared to vehicle-treated animals, and an antimetastatic effect that was fully reversed by a neutralizing antibody against ICAM-1 [% metastatic lung nodules vs. isotype control (100%): 47.7% for CBD + isotype antibody and 106.6% for CBD + ICAM-1 antibody]. (nih.gov)
- Tissue inhibitor of metalloproteinases 2 (TIMP2) is a gene and a corresponding protein. (wikipedia.org)
- In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. (wikipedia.org)
- As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. (wikipedia.org)
- Utilization of a novel recombinant myoglobin fusion protein expression system to characterize the tissue inhibitor of metalloproteinase (TIMP)-4 and TIMP-2 C-terminal domain and tails by mutagenesis. (wikipedia.org)
- The most efficacious protein signature in validation studies comprised osteopontin (OPN), resistin, matrix metalloproteinase 7 (MMP7) and interferon γ (IFNγ) as a four-marker panel while the addition of either CRP or adiponectin (ACRP-30) yielded comparable results in five protein signatures. (biomedcentral.com)
- Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. (biomedcentral.com)
- Materials and methods: Clonogenic survival assays and Western blot examinations were performed following telecobalt irradiation of cancer cells in the presence or absence of various combinations of PARP- and selective mitogen-activated protein kinase (MAPK) inhibitors. (jove.com)
- Our results indicate a direct link between COX-2 and activation of matrix degrading metalloproteinase enzymes. (pnas.org)
- Small molecules that inhibit a broad spectrum of metalloproteinases have not proved useful in the treatment of various diseases, probably due to the diverse roles of this large family of enzymes. (biologicalworld.com)
- Matrix metalloproteinases (MMPs) are extracellular enzymes. (aacrjournals.org)
- Matrix Metalloproteinases (MMP) are a family of zinc dependent enzymes responsible for degradation of ECM including basement membrane collagen, interstitial collagens, Fibronectin (FN), and various proteoglycans both in physiological and pathological conditions . (scirp.org)
- Extracellular matrix-degradative enzymes, including the matrix metalloproteinases (MMPs) MMP-2 and MMP-9, are thought to play key roles in angiogenesis by binding to docking sites on the cell surface after activation by plasmin- and/or membrane-type (MT) 1-MMP-dependent processes. (rupress.org)
- Excessive or unopposed exposure of the connective tissue to the neutrophils' enzymes causes its destruction. (biomedcentral.com)
- The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix. (biovendor.com)
- Mast cell activation in vivo is often associated with areas of oedema and connective-tissue degradation. (wiley.com)
- Since we have no evidence that mast cells express these four metalloenzymes, the release of mast cell serine proteinases following activation/degranulation could contribute to local metalloproteinase activation and subsequent matrix degradation. (wiley.com)
- IGFBP-3 proteolysis assays demonstrated that IGFBP-3 degradation was lower in TIMP-1-overexpressing livers, and zymography showed that matrix metalloproteinases (MMPs) were present in the liver homogenates and were capable of degrading IGFBP-3. (rupress.org)
- Besides degradation of the ECM, MMPs release bioactive molecules from the matrix or cell surface and play important role in tissue repair after injury, development and in a number of pathologies including arthritis and cancer metastasis. (biologicalworld.com)
- Inhibitor treatment prevented the fibronectin-network degradation, as well as the induction of the genes for peroxisome-proliferator-activated receptor γ and adipsin, two adipocyte phenotype markers. (portlandpress.com)
- The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. (scielo.br)
- Systolic dysfunction in Akita/ACE2KO mice was linked to enhanced activation of NADPH oxidase and metalloproteinases, resulting in greater oxidative stress and degradation of the extracellular matrix. (ahajournals.org)
- One example of ectopic activity of an otherwise normal function is collagenolytic degradation of basement membrane and extracellular matrix by secreted matrix metalloproteinases (MMPs). (google.com)
- Immunohistochemistry was performed on paraffin-embedded tissue specimens from 173 invasive breast carcinomas to detect the proteins TIMP-3, estrogen receptor (ER), progesterone receptor, p53, c-erbB-2, topoisomerase IIα and Bcl-2. (biomedcentral.com)
- Moreover, TIMP-3 immunopositivity was inversely correlated with the expression of p53 and topoIIα proteins ( p = 0.002 and p = 0.008, respectively), whereas it was positively associated with Bcl-2 expression ( p = 0.020). (biomedcentral.com)
- Because the activity of IGFs is controlled by IGF-binding proteins (IGFBPs), we investigated whether TIMP-1 overexpression altered the IGFBP status in the transgenic liver. (rupress.org)
- PARP-inhibitor treatment prevents hypertension induced cardiac remodeling by favorable modulation of heat shock proteins, Akt-1/GSK-3? (jove.com)
- The presence of the inhibitor in isolated PMNL could also be demonstrated by indirect immunofluorescence using a specific antibody against TIMP-1. (uni-bielefeld.de)
- Furthermore, treatment with the EGFR specific inhibitor PD-168393 or the EGF-neutralizing antibody decreased cardiomyocyte proliferation as well as phosphorylation of JNK and SP-1 in both WT and TIMP-3 −/− cardiomyocytes. (physiology.org)
- These results define new biological activities of IL-6 and provide further insight into the regulation of connective tissues by cytokines. (scripps.edu)
- In addition, connective tissues and muscular tissues enable the vaginal wall to have enough strength and toughness to maintain the normal anatomic position and function [ 3 - 5 ]. (hindawi.com)
- The specific species of ECM of connective tissues often differ chemically, but collagen generally forms the bulk of the structure. (wikipedia.org)
- Balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in the cervical mucus plug estimated by determination of free non-complexed TIMP. (uni-bielefeld.de)
- The balance between matrix metalloproteinases (MMP) and their inhibitors must be tightly regulated during CNS inflammation. (unt.edu)
- To define domains of tissue inhibitor of metalloproteinases (TIMP-1) that are important to its ability to inhibit fibroblast-type collagenase (FIB- CL), two different approaches were used: (i) competition with synthetic peptides modeled after the human TIMP-1 sequence and (ii) localization of epitopes of blocking antibodies. (elsevier.com)
- Here, we investigated whether increased TIMP-1 levels in the liver achieved by adenoviral gene transfer will effectively inhibit liver metastasis in two independent animal models TIMP-1 was transferred with adenoviral vectors into the livers of DBA/2 and Balb/c mice, which were subsequently challenged by hematogenous experimental metastases of the T-cell lymphoma cell line L-CI.5s or the colorectal carcinoma cell line CT-26, respectively. (fu-berlin.de)
- Adenoviral gene transfer led to systemic and local TIMP-1 levels sufficient to inhibit metastasis of a highly aggressive T-cell lymphoma, pointing at the requirement of threshold levels for effective anti-metastatic efficacy. (fu-berlin.de)
- Cannabinoids inhibit cancer cell invasion via increasing tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). (nih.gov)
- Disclosed herein are compounds which inhibit the expression of matrix metalloproteinases in cells. (google.com)
- TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. (ox.ac.uk)
- In animal models, low dose pioglitazone inhibits lesion progression and matrix metalloproteinase expression in advanced atherosclerotic plaques. (clinicaltrials.gov)
- Together, these results provide evidence that TIMP-1 inhibits liver hyperplasia, an early event in TAg-mediated tumorigenesis, by reducing the activity of the tumor-inducing mitogen, IGF-II. (rupress.org)
- We conclude that TIMP-3 inhibits neonatal mouse cardiomyocyte proliferation by upregulating p27 expression. (physiology.org)
- Decreased TIMP-1 and TIMP-2 expression in the extracellular matrix of the walls of AAAs has been shown in several studies. (springer.com)
- The expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) is required for normal development of zebrafish embryos. (nih.gov)
- Functional studies showed that the balance of TIMP-2 expression is important to normal development as reflected by the fact that both blockage of TIMP-2 translation using antisense morpholino oligonculeotides or increased translation of TIMP-2 using a mRNA microinjection approach resulted in abnormal zebrafish development. (nih.gov)
- A detailed knowledge of the mechanisms controlling TIMP gene expression is therefore important. (biochemj.org)
- Differential expression of matrix metalloproteinases and tissue-derived inhibitors of metalloproteinase in fetal and adult skins. (uni-bielefeld.de)
- Expression of matrix metalloproteinases and their endogenous tissue inhibitors in skin lesions from patients with tuberous sclerosis. (uni-bielefeld.de)
- Here, we investigated downstream effects of HIV-1 Tat and gp120 expression in astrocytes on the TIMP-1/MMP balance. (unt.edu)
- Deficiency in TIMP-3 decreased p27 expression and increased cardiomyocyte proliferation in cardiomyocytes and neonatal hearts. (physiology.org)
- Treatment with recombinant TIMP-3 decreased JNK phosphorylation and EGFR expression/phosphorylation. (physiology.org)
- Acetylation in the regulation of metalloproteinase and tissue inhibitor of metalloproteinases gene expression. (biologicalworld.com)
- An alternative therapeutic approach for a number of pathologies is to modulate the expression of specific metalloproteinase genes. (biologicalworld.com)
- We discuss the suggestion that HDACi may act in a dual fashion: selectively decreasing cancer cell viability and reducing metastatic potential by decreasing stromal cell expression of specific metalloproteinases. (biologicalworld.com)
- Further, changes in a subset of circulating cytokines were not matched by their changes in muscle, but instead reflected altered expression in liver and adipose tissues. (mcponline.org)
- Recombinant Human Tissue Inhibitor of Metalloproteinases 1 is produced by our Mammalian expression system and the target gene encoding Cys24-Ala207 is expressed with a 6His tag at the C-terminus. (absin-reagent.com)
- The aims of this study were to assess the prevalence and clinical significance of MMP and TIMP expression in invasive breast cancer and to determine its association with immunohistochemical-based molecular classification. (biomedcentral.com)
- We found some variations in MMP and TIMP expression among the immunohistochemical-based molecular subtypes of breast carcinomas, suggesting differences in their tumor pathophysiology. (biomedcentral.com)
- Additional studies are needed to determine the mechanisms underlying the differences of MMP and TIMP expression in the molecular subtypes for the development of specific therapeutic targets for breast cancer subtypes. (biomedcentral.com)
- Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. (jneurosci.org)
- The results of the present study revealed that, during silicosis development, ACE/Ang II/AT1 expression in local lung tissues increased, whereas that of Ac‑SDKP decreased. (spandidos-publications.com)
- Compared with the silicosis group, the expression of α‑smooth muscle actin (α‑SMA), Collagen (Col) I, Fibronectin (Fn) and AT1 were significantly downregulated, whereas matrix metalloproteinase‑1 (MMP‑1) expression and the MMP‑1/tissue inhibitor of metalloproteinases‑1 (TIMP‑1) ratio was increased in the Ac‑SDKP treatment group. (spandidos-publications.com)
- In addition, MMP‑1 expression and the MMP‑1/TIMP‑1 ratio were significantly higher in Ac‑SDKP and valsartan pre‑treatment groups compared with the Ang II group. (spandidos-publications.com)
- We found that PFIO suppressed the migration and invasive ability of A549 cells while decreasing the expression levels and activity of matrix metalloproteinase (MMP)-2 and MMP-9. (spandidos-publications.com)
- Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine gene expression of MMP9 and the tissue inhibitors of metalloproteinases TIMP1 and TIMP2. (bmj.com)
- However, coincident with the expression of tissue-invasive or morphogenic processes, secreted MMP-2 and MMP-9 are activated. (rupress.org)
- We have investigated the expression and activity of MMP-7 and TIMP-1 in the hippocampus following kainic acid-induced injury, the relationship of this enzyme-inhibitor system to proNGF processing, and the consequences for p75 NTR -mediated apoptosis in vitro and in vivo . (jneurosci.org)
- In this study, we investigate the role of synovial macrophages and their main proinflammatory cytokines, interleukin (IL)-1 and tumour necrosis factor-alpha (TNF-α), in driving osteoarthritis synovitis and influencing the production of other pro- and anti-inflammatory cytokines, production of matrix metalloproteinases, and expression of aggrecanases in the osteoarthritis synovium. (biomedcentral.com)
- Electroacupuncture also led to a significant decrease of matrix metalloproteinase-2 (MMP-2) expression and an increase of tissue inhibitor of MMP (TIMP-2) expression. (medsci.org)
- Additionally, the expression of semaphorin 3A (Sema3A) and nerve growth factor receptor (NGFR) p75 in TNBC tissue was significantly upregulated in response to electroacupuncture. (medsci.org)
- Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells. (rupress.org)
- p53 was also shown to positively regulate the expression of thrombospondin-1 (TSP-1), a physiological inhibitor of angiogenesis, in fibroblasts of Li-Fraumeni patients ( 14 ). (rupress.org)
- Compared with messenger RNA, miRNA expression profiles better classify undifferentiated tumors, which indicates that miRNAs are more tissue-specific and more accurately reflect the characteristics of certain tumors 5 . (jcancer.org)
- In the initial events of wound healing, collagen III predominates in the granulation tissue which later on in remodeling phase gets replaced by collagen I giving additional tensile strength to the healing tissue. (wikipedia.org)
- Western blotting was used to identify a specific MMP, MMP2 (a gelatinase that digests basement membrane collagen and the dominant MMP observed on zymography) and a specific TIMP, TIMP2. (bmj.com)
- During angiogenesis, endothelial cells initiate a tissue-invasive program within an interstitial matrix comprised largely of type I collagen. (rupress.org)
- To identify proteinases critical to neovessel formation, an ex vivo model of angiogenesis has been established wherein tissue explants from gene-targeted mice are embedded within a three-dimensional, type I collagen matrix. (rupress.org)
- To identify the proteolytic systems required for neovessel formation within a physiologically relevant interstitial matrix, three-dimensional (3-D) gels of cross-linked type I collagen were seeded with tissue explants or endothelial cells isolated from mice harboring inactivating mutations in either the plasminogen, MMP-2 , MMP-9 , β 3 integrin , CD44 , or MT1-MMP genes. (rupress.org)
- The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl 4 treated animals with an ELISA detecting a fragment of type III collagen generated in vitro by MMP-9 (C3M), known to be associated with liver fibrosis and to investigate cAMP modulation of MMP activity and liver tissue turnover in this model. (biomedcentral.com)
- RT-PCR demonstrated the presence of mRNA for metalloproteinase inhibitors TIMP1 and TIMP2 in PSCs while reverse zymography revealed the presence of functional TIMP2 in PSC secretions. (bmj.com)
- Pancreatic stellate cells have the capacity to synthesise a number of matrix metalloproteinases, including MMP2, MMP9, and MMP13 and their inhibitors TIMP1 and TIMP2. (bmj.com)
- Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. (scirp.org)
- Blood sample was collected to analyze serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metalloproteinase 1 (TIMP1). (scirp.org)
- In addition to hormone receptor status and Ki-67, HER2/neu+ and topoisomerase-II-alpha status using fluorescence in situ hybridisation (FISH) and immunohistochemistry, TIMP-1 using immunohistochemistry, and aneuploidy of chromosome 17 using FISH were evaluated and correlated with outcome and taxane benefit. (springer.com)
- In contrast, MMP-2 lacks a serine protease recognition motif ( 10 ) and is activated at the cell surface of invasive cells by a multimeric receptor/activation complex consisting of the tissue inhibitor of metalloproteinase 2 (TIMP-2), the membrane type 1 MMP (MT1-MMP), and integrin αvβ3 ( 11 ). (pnas.org)
- a TIMP-2/MT1-MMP receptor complex and a TIMP-2-free MT1-MMP processing enzyme that initiates MMP-2 activation by cleaving the N-terminal propeptide. (pnas.org)
- A TIMP-3/epidermal growth factor (EGF) receptor (EGFR)/c-Jun NH 2 -terminal kinase (JNK)/SP-1/p27 pathway was investigated. (physiology.org)
- The indispensable roles of mesenchymal/stromal androgen receptor (AR) for the prostate organogenesis have been demonstrated by using tissue recombination from wild-type and testicular feminized mice. (wiley.com)
- This contraction was also inhibited by ethacrynic acid, by inhibitors of Na+, K+-ATPase (ouabain), Ca2+- ATPase (thapsigargin), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, by a non-selective phosphodiesterase inhibitor (papaverine), and by adenosine A2 (metrifudil), and cannabinoid receptor (CP-55940) agonists. (omicsonline.org)
- Here, we demonstrate the use of a noncatalytic fragment of matrix metalloproteinase 2 (termed PEX) delivered by lentiviral vectors in different angiogenesis models. (pnas.org)
- Lentiviral delivery of PEX blocked basic fibroblast growth factor-induced matrix metalloproteinase 2 activation and angiogenesis on chicken chorioallantoic membranes. (pnas.org)
- During angiogenesis, invasive endothelial cells recruit matrix metalloproteinases (MMPs) to remodel the extracellular matrix and the basal lamina-an important physical barrier between the endothelial and connective tissue ( 3 , 4 ). (pnas.org)
- Most diseases that cause catastrophic loss of vision do so as a result of abnormal angiogenesis and wound healing, often in response to tissue ischemia or inflammation. (jci.org)
- This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors. (rupress.org)
- The switch to the angiogenic phenotype of a tumor is thought to result from a shift in the balance between the secretion of angiogenesis inducers and inhibitors. (rupress.org)
- Furthermore, p53-null glioblastoma cells are able to release an inhibitor of angiogenesis, called glioma-derived angiogenesis inhibitory factor (GD-AIF), upon restoration of wt p53 function ( 13 ). (rupress.org)
- Walker 256 cancer cells secrete tissue inhibitor of metalloproteinase-free metalloproteinase-9. (uni-bielefeld.de)
- Activated macrophages within the arterial wall secrete matrix-degrading metalloproteinases (MMPs) that weaken the atherosclerotic plaque and contribute to its fissuration. (aspetjournals.org)
- This is in contrast to murine knockout studies that indicate that TIMP-2 does not have a major role in mouse embryogenesis. (nih.gov)
- The region hybridizing with a murine TIMP-1 promoter fragment has been subcloned and analysed further. (biochemj.org)
- Transient transfection of promoter-chloramphenicol O -acetyltransferase reporter constructs into primary human connective tissue fibroblasts shows that a 904 bp fragment that hybridizes to a murine TIMP-1 promoter fragment contains a functional promoter. (biochemj.org)
- Murine tissue inhibitor of metalloproteinases-1 (mTIMP-1) was expressed in baculovirus-infected insect cells (Sf9). (uni-bielefeld.de)
- Using a double transgenic murine hepatic tumor model, we demonstrate that tissue inhibitor of metalloproteinase 1 (TIMP-1) blocks liver hyperplasia during tumor development, despite TAg-mediated reactivation of IGF-II. (rupress.org)
- Molecular dynamics (MD) simulations reveal that the high-affinity TIMP-1 mutants exhibit significantly reduced binding interface flexibility and more stable hydrogen bond networks. (rcsb.org)
- Consequently, a good understanding of the broader contexts - from the molecular, to the cellular and tissue levels - in which such molecular complexes operate will provide essential insights into direct new drug developments. (dovepress.com)
- Matrix metalloproteinases (MMPs) are critical for metastasis of tumor cells. (fu-berlin.de)
- Tissue inhibitor of metalloproteinases-1 (TIMP-1), a natural MMP inhibitor, was shown to reduce metastasis in different models. (fu-berlin.de)
- TIMP-1, a key inhibitor of MMP-9, was expressed at 10^5-fold higher levels by adenoviral gene transfer as compared with levels achieved in TIMP-1 transgenic mice, previously shown to be inefficient to reduce T-cell lymphoma metastasis. (fu-berlin.de)
- High local and systemic (serum) levels of TIMP-1 led to substantial (94%) reduction of T-cell lymphoma and colorectal carcinoma (73%) experimental liver metastasis. (fu-berlin.de)
- The medical literature contains an increasing number of manuscripts illustrating that the launched concepts and clinical uses of MMP inhibitors against cancer cell invasion and metastasis were too simple and, in fact, wrong. (dovepress.com)
- Armstrong TS, Prabhu S, Aldape K, Hossan B, Kang S, Childress A, Tolentino L, Gilbert MR (2011) A case of soft tissue metastasis from glioblastoma and review of the literature. (springer.com)
- TIMP-1/MMP-9 imbalance in an EBV-immortalized B lymphocyte cellular model: evidence for TIMP-1 multifunctional properties. (uni-bielefeld.de)
- Similar to other secreted MMPs, the latent proenzyme of MMP-2 is activated by its association with TIMP-2 (23 , 24) and cell surface-anchored MT1-MMP (25 , 26) , and a stoichiometric imbalance in this ternary complex may be associated with tumor progression. (aacrjournals.org)
- The upregulation of TIMP-1 after seizure and other pathological conditions suggests that an imbalance between MMP-7 and TIMP-1 may influence neuronal death by enhancing levels of proNGF. (jneurosci.org)
- The current pathogenetic theories for the development of COPD include an imbalance between the protease and antiprotease system, dysregulation of oxidant-antioxidant activity and chronic airway inflammation, processes that lead to the progressive destruction and abnormal repair of the lung connective tissue matrix. (bmj.com)
- When TIMP-1 was allowed to react with human neutrophil elastase, its inhibitory activity was destroyed. (biochemj.org)
- Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. (ox.ac.uk)
- However, cleavage of this bond by neutrophil elastase was prevented when TIMP-1 formed a complex with the catalytic domain of MMP-3, and full TIMP-1 activity was restored after dissociation of the complex at pH 3.0 in the presence of EDTA. (biochemj.org)
- Among a series of monoclonal and polyclonal antibodies (mAbs and pAbs) to TIMP-1, we identified two, one mAb and one pAb, that neutralized the activity of TIMP-1 against FIB-CL. (elsevier.com)
- Effects of different preparations of IL-6 on production of collagenase and tissue inhibitor of metalloproteinases-1/erythroid potentiating activity production are studied in human fibroblasts, synoviocytes, and articular chondrocytes. (scripps.edu)
- IL-6, however, is identified as a potent inducer of de novo synthesis of tissue inhibitor of metalloproteinases-1/erythroid potentiating activity in all types of connective tissue cells examined. (scripps.edu)
- PEGylation extends circulation half-life while preserving in vitro and in vivo activity of tissue inhibitor of metalloproteinases-1 (TIMP-1). (uni-bielefeld.de)
- The MMP inhibitor, BB-94, blocked MMP-2 activity and invasion associated with Akt1- and v-akt-expressing cells. (aacrjournals.org)
- MMP-7 activity is inhibited by tissue inhibitor of metalloproteinase 1 (TIMP-1). (jneurosci.org)
- We demonstrate that seizures decrease MMP-7 and increase TIMP-1, attenuating cleaving activity and leading to increased proNGF and p75 NTR activation. (jneurosci.org)
- Accumulation of extracellular matrix (ECM) and increased matrix metalloproteinase (MMP) activity are hallmarks of liver fibrosis. (biomedcentral.com)
- Recently, we identified an unexpected role for matrix metalloproteinases (MMPs) * in fibrin-invasive activity ( 3 ). (rupress.org)
- Biochemical changes associated with this phenotypic change included activation of metalloproteinase-2 and increased RNA levels for the membrane-type metalloproteinase. (pnas.org)
- The MT1-MMP-independent process was sensitive to MMP inhibitors that target membrane-anchored MMPs, and further studies identified MT2-MMP and MT3-MMP, but not MT4-MMP, as alternate pro-invasive factors. (rupress.org)
- The complex of latent MMP-2 (pro-MMP-2)with TIMP-2 serves to facilitate the activation of pro-MMP-2 at the cell surface by MT1-MMP (MMP-14), a membrane-anchored MMP. (wikipedia.org)
- Proteolysis and interruption of the basement membrane requires activation of specialized matrix metalloproteinases which selectively degrade basement membrane collagens type IV and V, the type IV collagenases or gelatinases (MMPs). (google.com)
- Effect of Pioglitazone on Tissue Inhibitor of Metalloproteinases 3 (TIMP-3) and TNF (Tumor Necrosis Factor)-α Converting Enzyme (TACE) in Skeletal Muscle and Their Circulating Substrates. (clinicaltrials.gov)
- The present market of successful biologicals contains many monoclonal antibodies, such as signaling inhibitors, with antitumor necrosis factor (anti-TNF) being the flagship of an armada. (dovepress.com)
- The matrix metalloproteinases (MMP) are purported to degrade almost all connective tissue elements and are secreted by cells in the form of inactive precursors. (wiley.com)
- Matrix metalloproteinase belong to family of pericellular collagenases which degrade extracellular matrix (ECM), and is involved in the modulation and susceptibility of various cancers. (cdc.gov)
- The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. (biologicalworld.com)
- Twenty-three DE genes encoding trypsins, metalloproteinases, and serine-type endopeptidases were significantly upregulated in midguts of mosquitoes at day 1 following SM or PM ingestion. (biomedcentral.com)
- Materials and Methods: Levels of PAI-1, MMP-3, MMP-8, TIMP-1 and TIMP-2 in 35 patients with post-cholecystectomy BDI by complete biliary obstruction were measured and compared to a healthy control group. (scirp.org)
- Tissue inhibitor of metalloproteinases 2 levels are increased in the hearts of patients with aortic valvular stenosis 16 and patients with pressure-overloaded cardiomyopathy. (ahajournals.org)
- The proteasome inhibitor, lactacystin, markedly increased MMP-2 levels and invasion in control cells but not in Akt1- and v-akt-expressing cells. (aacrjournals.org)
- More consistently, GH replacement reduces body fat and visceral adipose tissue, reduces low-density lipoprotein cholesterol and triglyceride levels, and improves endothelial function. (biomedsearch.com)
- Endogenous protease inhibitor uptake within the graft during reperfusion in human liver transplantation. (uni-bielefeld.de)
- We propose that viral gene transfer of TIMP-1 can provide a suitable defense strategy to prevent metastatic spread to the liver. (fu-berlin.de)
- While the causes of liver cirrhosis are multifactorial, there are some pathological characteristics that are common to all cases of cirrhosis, including degeneration and necrosis of hepatocytes, replacement of healthy liver parenchyma by fibrotic scar tissues and regenerative nodules, and loss of liver function [ 4 - 7 ]. (intechopen.com)
- Our fibrosis research works across multiple tissues and disease types including liver, lung, kidney, heart, skin and joints. (ncl.ac.uk)
- From the 19 best predictive clusters, 2-3 biomarkers were selected based on their pathophysiological profile (chemoattractants, inflammation, tissue destruction and repair) and the statistical significance of their relationship with clinically important end points was tested. (bmj.com)
- In response to tissue damage, inflammation, or neoplastic growth, a provisional matrix largely composed of cross-linked fibrin and fibronectin is deposited at the affected site ( 1 , 2 ). (rupress.org)
- However, in the absence of specific MT1-MMP inhibitors or gene-deleted animals, the functional importance of this metalloproteinase in a physiologically relevant cell population has remained the subject of conjecture. (rupress.org)
- In severe cases, the excess tissue may cover the crowns of the teeth, thus causing functional, esthetic, and periodontal problems, such as bone loss and bleeding, due to the presence of pseudopockets and plaque accumulation. (biomedcentral.com)
- E xtracellular matrix (ECM) 1 serves as the immediate microenvironment for interactions with the cell surface, besides providing the structural support for all tissues. (rupress.org)
- Structural selectivity - in fact, the lack thereof - has been invoked as an explanation for the failure of matrix metalloproteinase (MMP) inhibitors as oncology drugs. (dovepress.com)
- Cross-linked fibrin is deposited in tissues surrounding wounds, inflammatory sites, or tumors and serves not only as a supporting substratum for trafficking cells, but also as a structural barrier to invasion. (rupress.org)