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 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-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.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.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.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Matrix Metalloproteinase Inhibitors: Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.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 Metalloproteinases: A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.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.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).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.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 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 Metalloproteinase 7: The smallest member of the MATRIX METALLOPROTEINASES. It plays a role in tumor progression.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.Matrix Metalloproteinase 8: A member of the MATRIX METALLOPROTEINASES that cleaves triple-helical COLLAGEN types I, II, and III.HIV Protease: Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.Matrix Metalloproteinase 12: A secreted matrix metalloproteinase which is highly expressed by MACROPHAGES where it may play a role in INFLAMMATION and WOUND HEALING.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.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.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.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.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.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.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.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.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.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 Metalloproteinases, Secreted: A subclass of matrix metalloproteinases that are secreted into the pericellular space.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.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 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.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 3.4.24.3.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.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.Phenylmercuric Acetate: A phenyl mercury compound used mainly as a fungicide. Has also been used as a herbicide, slimicide, and bacteriocide.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Protease La: A prokaryotic ATP-dependent protease that plays a role in the degradation of many abnormal proteins. It is a tetramer of 87-kDa subunits, each of which contains a proteolytic site and a ATP-binding site.Cysteine Proteases: A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.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.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.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.ATP-Dependent Proteases: Proteases that contain proteolytic core domains and ATPase-containing regulatory domains. They are usually comprised of large multi-subunit assemblies. The domains can occur within a single peptide chain or on distinct subunits.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.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.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.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 3.4.24.14.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.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.Kinetics: The rate dynamics in chemical or physical systems.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).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.Dipeptides: Peptides composed of two amino acid units.Protease Nexins: Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.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.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.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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.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).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.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.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.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Mice, Inbred C57BLMolecular Weight: The sum of the weight of all the atoms in a molecule.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Matrix Metalloproteinase 20: A secreted matrix metalloproteinase that is the predominant proteolytic activity in the enamel matrix. The enzyme has a high specificity for dental enamel matrix protein AMELOGENIN.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.HemopexinDisease 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.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.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.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.ThiophenesBlotting, 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.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.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 3.4.21.36.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.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.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.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.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.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.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Chondrocytes: Polymorphic cells that form cartilage.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.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.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.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.Oligopeptides: Peptides composed of between two and twelve amino acids.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Proteoglycans: Glycoproteins which have a very high polysaccharide content.Transforming 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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.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.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.Tumor 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.Hydroxamic Acids: A class of weak acids with the general formula R-CONHOH.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 3.4.21.37.Subtilisins: A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-Matrix Metalloproteinase 17: A membrane-type metalloproteinase that is associated with the CELL MEMBRANE via a GLYCOSYL-PHOSPHATIDYLINOSITOL linkage. It is synthesized as an inactive zymogen that is activated by the action of PROPROTEIN CONVERTASES such as FURIN.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.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.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.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.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.ElastinEscherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.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.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.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.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.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Cell Adhesion: Adherence of cells to surfaces or to other cells.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.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.Bacterial Proteins: Proteins found in any species of bacterium.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.)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.Doxycycline: A synthetic tetracycline derivative with similar antimicrobial activity.Furin: A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.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.Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.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.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.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)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)Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.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.Synovial Fluid: The clear, viscous fluid secreted by the SYNOVIAL MEMBRANE. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.Protein PrecursorsVascular 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.Ubiquitin-Specific Proteases: Members of the peptidase C19 family which regulate signal transduction by removing UBIQUITIN from specific protein substrates via a process known as deubiquitination or deubiquitylation.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).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.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Endopeptidase Clp: An ATP-dependent protease found in prokaryotes, CHLOROPLASTS, and MITOCHONDRIA. It is a soluble multisubunit complex that plays a role in the degradation of many abnormal proteins.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.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)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.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.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The MMPs are inhibited by specific endogenous tissue inhibitor of metalloproteinases (TIMPs), which comprise a family of four ... Matrix metalloproteinases combines with the metal binding protein, metallothionine; thus helping in metal binding mechanism. ... Proteases in angiogenesis Drug discovery and development of MMP inhibitors Verma RP, Hansch C (March 2007). "Matrix ... This determines substrate specificity and is the site for interaction with TIMP's (tissue inhibitor of metalloproteinases). The ...
It is a serine protease inhibitor (serpin) protein (SERPINE1). The other PAI, plasminogen activator inhibitor-2 (PAI-2) is ... that functions as the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of ... Plasmin mediates the degradation of the extracellular matrix either by itself or in conjunction with matrix metalloproteinases ... mapping the binding sites on PAI-1 and Vn". Biological Chemistry. 383 (7-8): 1143-9. doi:10.1515/BC.2002.125. PMID 12437099. ...
By blocking TSP1 from binding to its cell surface receptor (CD47) normal tissue becomes nearly immune to cancer radiation ... It also interacts with numerous proteases involved in angiogenesis, including plasminogen, urokinase, matrix metalloproteinase ... It is a multi-domain matrix glycoprotein that has been shown to be a natural inhibitor of neovascularization and tumorigenesis ... Bound protein fragments of the type I repeats have been shown to serve as attachment factors for both ECs and melanoma cells. ...
Like ADAMTS5, it can be effectively inhibited by tissue inhibitor of metalloproteinase-3 (TIMP3) and this inhibition can be ... a novel family of proteases with an ADAM protease domain and thrombospondin 1 repeats". FEBS Letters. 445 (2-3): 223-5. doi: ... The TSR is important for binding of the enzyme to the extracellular matrix and hence its substrate specificity. Adjacent to the ... A disintegrin and metalloproteinase with thrombospondin motifs 4 is an enzyme that in humans is encoded by the ADAMTS4 gene. ...
13 KD serine protease, or 24KD endopeptidase. Angiostatin is known to bind many proteins, especially to angiomotin and ... It is an endogenous angiogenesis inhibitor (i.e., it blocks the growth of new blood vessels), and it is currently undergoing ... Furthermore, angiostatin can be cleaved from plasminogen by different metalloproteinases (MMPs), elastase, prostate-specific ... endothelial cell surface ATP synthase but also integrins, annexin II, C-met receptor, NG2 proteoglycan, tissue-type plasminogen ...
Endogenous inhibitors of angiogenesis are present in both normal tissue and cancerous tissue. Overall, endostatin down ... Endostatin also binds all heparan sulfate proteoglycans with low affinity. Oligomeric endostatin (trimer or dimer) binds mainly ... Endostatin may prevent activity from certain metalloproteinase. Several studies have focused on the downstream effects of ... by proteases such as cathepsins. Collagen is a component of epithelial and endothelial basement membranes. Endostatin, as a ...
The metalloproteinase inhibitors (MPIs) can prevent unwanted proteolysis by denaturing their target proteases through non- ... Even though zinc-binding metalloproteinases have been found to aid processes such as protein turnover and embryogenesis, it is ... MMPs are synthesized primarily by connective tissues and have a large contribution to the initial events of tissue degradation ... Protein inhibitors of proteases, are present in plants, animals, and microorganisms. They are ubiquitous in nature and have a ...
... at various levels for example by endogenous inhibitors like α2-macroglobulin and the tissue inhibitors of metalloproteinases ( ... Most MMP inhibitors are chelating agents. The inhibitor binds to the zinc at the active center of the enzyme, thereby blocking ... Other inhibitor mechanisms are possible.α2-Macroglobulin (α2M) is a protease inhibitor which inhibits activated MMPs. α2M and ... Protein inhibitors such as α2-macroglobulin are known to work with metalloproteinases. The first generation of MMP inhibitors ...
... tissue inhibitor of metalloproteinase complexes in cancer". Cancer. 76 (4): 700-8. doi:10.1002/1097-0142(19950815)76:4. 3.0.co; ... snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies ... Activation is achieved through an interacting protease cascade involving plasmin and stromelysin 1 (MMP-3). Plasmin generates ... Complexes of Gelatinase B/Tissue Inhibitors of Metalloproteinases are seen to be increased in gastrointestinal cancer and ...
These defects weaken connective tissue (the tissue that binds and supports the body's muscles, ligaments, organs, and skin), ... 2004). "Expression profiling of metalloproteinases and their inhibitors in cartilage". Arthritis Rheum. 50 (1): 131-41. doi: ... a novel family of proteases with an ADAM protease domain and thrombospondin 1 repeats". FEBS Lett. 445 (2-3): 223-5. doi: ... A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAM-TS2) also known as procollagen I N-proteinase (PC I-NP) ...
Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for ... In two 2006 studies, another gene that has implications for the disease, called HTRA1 (encoding a secreted serine protease), ... lipoprotein lipase and the ATP-binding cassette A1 correlate with disease progression. The early stigmata of disease, drusen, ... Six mutations of the gene SERPING1 (Serpin Peptidase Inhibitor, Clade G (C1 Inhibitor), Member 1) are associated with AMD. ...
Cathepsin S is a cysteine protease that moderately attenuates binding of FGF-positive cells to a perlecan-positive substrate. ... Timing of gene expression during development varies from tissue to tissue. Basement membranes are often the driving force ... Perlecan is a potent inhibitor of smooth muscle cell proliferation and is thus thought to help maintain vascular homeostasis. ... In a model of explant growth in vitro using corneal epithelium, Matrix Metalloproteinase (MMP) 2 expression correlates with an ...
It is thought its similarity to thyropin-type cysteine protease inhibitors suggests its function may be related to protease ... Kohfeldt E, Maurer P, Vannahme C, Timpl R (1997). "Properties of the extracellular calcium binding module of the proteoglycan ... Nakada M, Miyamori H, Yamashita J, Sato H (2003). "Testican 2 abrogates inhibition of membrane-type matrix metalloproteinases ... 2001). "Distribution of testican expression in human brain". Cell Tissue Res. 302 (2): 139-44. doi:10.1007/s004410000277. PMID ...
"Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type 1- ... and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. TIMP2 functions as both an ... 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 ...
Koziel, Joanna; Potempa, Jan (2013-02-01). "Protease-armed bacteria in the skin". Cell and Tissue Research. 351 (2): 325-337. ... Aureolysin cleaves and inactivates protease inhibitor α1-antichymotrypsin and partially inactivate α1-antitrypsin, de- ... It also mediates cleavage of clumping factor B causing loss of binding of S. aureus to fibrinogen. By this it may act as a self ... degradation of Staphylococcus aureus' metalloproteinase". Biochim. Biophys. Acta. 993: 301-304. doi:10.1016/0304-4165(89)90181- ...
Quiescent PaSCs produce metalloproteinases such as MMP-2, MMP-9, and MMP-13 and their inhibitors, which assist in the turnover ... Camostat mesilate, an oral protease inhibitor, that is used to treat patients with chronic pancreatitis inhibited the ... Connective tissue growth factor is involved in the pathogenesis of fibrotic diseases and is predominantly found in PaSCs ... Indian Hedgehog binding results in relocation of the transcriptional of transcription factor Gli-1 into the nucleus, inducing ...
... designed after protease inhibitor mechanisms, lends ABPs their specificity towards targeting active proteases. Once bound, the ... tissue, or organism. Dr. Overall's group would go on to annotate the complete human and mouse protease-inhibitor degradomes in ... Elevated membrane-type matrix metalloproteinases in gliomas revealed by profiling proteases and inhibitors in human cancer ... For proteases, specific probes for protease genes and their inhibitors have been developed to view expression patterns on the ...
... and by endogenous inhibitors known as tissue inhibitors of metalloproteases (TIMPs). The role of matrix metalloproteases and ... a noncatalytic metalloproteinase fragment with integrin binding activity". Cell. 92 (3): 391-400. doi:10.1016/S0092-8674(00) ... Tissue plasminogen activator (tPA), and urokinase plasminogen activator (urokinase, uPA) are serine proteases which cleave and ... Along with ADAMs and MT-MMPs, membrane bound serine proteases also may play a role in ectodomain shedding. The formation of ...
These repeats bind extracellular matrix proteins, growth factors, proteases, protease inhibitor complexes, and other proteins ... "Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type 1 are internalized ... Notably, LRP1 functions in clearing proteases such as plasmin, urokinase-type plasminogen activator, and metalloproteinases, ... While membrane-bound LRP1 performs endocytic clearance of proteases and inhibitors, proteolytic cleavage of its ectodomain ...
Tissue Factor and tissue factor pathway inhibitor, Metalloproteinase 9, and fibronectin. The levels of PAK1 activity under ... Reversible covalent binding of IPA-3 to the PAK1 regulatory domain prevents GTPase docking and the subsequent switch to a ... and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases". Molecular Cell. 49 (4): 668-79. doi:10.1016/j.molcel. ... The core domains of the PAK family include a kinase domain in the C-terminal region, a p21-binding domain (PBD), and an auto- ...
MMP-2 is unlike other MMP's as its activity is modulated by metalloproteases called tissue inhibitor of metalloproteases (TIMP ... heparin-binding growth factors, chemokines and lipoproteins. HSPGs are prominent components of blood vessels. Binding to HS ... Matrix metalloproteinases (MMPs) MMP-2 is the main metalloprotease secreted by breast-cancer cells or induced in the adjacent ... There is increased expression of protease systems in cancer cells, to equip them with the tools necessary to degrade the ...
Plasmin, another type of protease, can either be bound by a plasmin inhibitor, or work to degrade fibrin clots, which is the ... regulation and functional role of the plasminogen activator and matrix metalloproteinase systems". Mol. Cell. Endocrinol. 187 ( ... "Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type 1 are internalized ... Ichinose A, Takio K, Fujikawa K (1986). "Localization of the binding site of tissue-type plasminogen activator to fibrin". J. ...
... inhibitor can be endogenous or come from outside as drug or a dietary component. Angiogenesis may be a target for ... Binding to VEGF receptor-2 (VEGFR-2) starts a tyrosine kinase signaling cascade that stimulates the production of factors that ... The presence of blood vessels where there should be none may affect the mechanical properties of a tissue, increasing the ... Second, the activated endothelial cells begin to release enzymes called proteases that degrade the basement membrane to allow ...
... for example matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Other diseases linked to ... Cysteine protease Serine protease Threonine protease Aspartic protease Glutamic protease Metalloprotease Asparagine peptide ... Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor". Cell. 89 (3): 331-340. doi: ... Proteases may be regulated by antiproteases or protease inhibitors, and imbalance between proteases and antiproteases can ...
... salivary proteins and aprotinin type protease inhibitors". The EMBO Journal. 9 (2): 385-93. PMC 551678 . PMID 1689238. Chu ML, ... The alpha 3 type VI chain has been shown to bind extracellular matrix proteins, an interaction that explains the importance of ... Other disorders involving muscle and connective tissue include weakness, joint laxity and contractures, and abnormal skin. ... "Cleavage of human corneal type VI collagen alpha 3 chain by matrix metalloproteinase-2". Cornea. 15 (5): 490-6. doi:10.1097/ ...
72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix (ECM) in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades type IV collagen, the major structural component of basement membranes. The enzyme plays a role in endometrial menstrual breakdown, regulation of vascularization and the inflammatory response. Activation of MMP-2 requires proteolytic processing. A complex of membrane type 1 MMP (MT1-MMP/MMP14) and tissue ...
72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix (ECM) in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades type IV collagen, the major structural component of basement membranes. The enzyme plays a role in endometrial menstrual breakdown, regulation of vascularization and the inflammatory response. Activation of MMP-2 requires proteolytic processing. A complex of membrane type 1 MMP (MT1-MMP/MMP14) and tissue ...
72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix (ECM) in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades type IV collagen, the major structural component of basement membranes. The enzyme plays a role in endometrial menstrual breakdown, regulation of vascularization and the inflammatory response. Activation of MMP-2 requires proteolytic processing. A complex of membrane type 1 MMP (MT1-MMP/MMP14) and tissue ...
The Design Structure Matrix (DSM; also referred to as dependency structure matrix, dependency structure method, dependency source matrix, problem solving matrix (PSM), incidence matrix, N2 matrix, interaction matrix, dependency map or design precedence matrix) is a simple, compact and visual representation of a system or project in the form of a square matrix. It is the equivalent of an adjacency matrix in graph theory, and is used in systems engineering and project management to model the structure of complex systems or processes, in order to perform system analysis, project planning and organization design. Don Steward coined the term "design structure matrix" in the 1960s, using the matrices to solve mathematical systems of equations. A design structure matrix lists all constituent subsystems/activities and the corresponding information exchange,interactions, and dependency patterns. For example, where the matrix elements represent activities, the matrix details what pieces of information are ...
Neutrophil collagenase, also known as matrix metalloproteinase-8 (MMP-8) or PMNL collagenase (MNL-CL), is a collagen cleaving enzyme which is present in the connective tissue of most mammals. In humans, the MMP-8 protein is encoded by the MMP8 gene. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is stored in secondary granules within neutrophils and is activated by autolytic cleavage. Its function is degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. GRCh38: Ensembl release 89: ...
Metaloproteinase matriks-2 (bahasa Inggris: gelatinase A, tissue gelatinase, type IV collagenase, matrix metalloproteinase 2, MMP-2, EC 3.4.24.24) merupakan enzim endopeptidase dengan berkas genetik MMP2,[1] yang disekresi ke dalam interstitium dan memiliki tambahan domain mirip fibronektin.[2] MMP-2 dahulu disebut MMP-5, memiliki Zn dan Ca sebagai kofaktor untuk mengiris gelatin tipe I, kolagen tipe IV, V, VII dan peptida mirip kolagen dengan urutan Pro-Gln-Gly-,-Ile-Ala-Gly-Gln.[3] Mutasi pada gen MMP2 dapat mengakibatkan sindrom Winchester dan sindrom NAO. Aktivitas MMP-2 terhambat oleh matlistatin A,[4] dan matlistatin B.[5] ...
72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene. The MMP2 gene is located on chromosome 16 at position 12.2. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix (ECM) in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades type IV collagen, the major structural component of basement membranes. The enzyme plays a role in endometrial menstrual breakdown, regulation of vascularization and the inflammatory response. Activation of MMP-2 requires proteolytic processing. A complex of membrane type 1 MMP (MT1-MMP/MMP14) and tissue ...
Metaloproteinase matriks-2 (bahasa Inggris: gelatinase A, tissue gelatinase, type IV collagenase, matrix metalloproteinase 2, MMP-2, EC 3.4.24.24) merupakan enzim endopeptidase dengan berkas genetik MMP2,[1] yang disekresi ke dalam interstitium dan memiliki tambahan domain mirip fibronektin.[2] MMP-2 dahulu disebut MMP-5, memiliki Zn dan Ca sebagai kofaktor untuk mengiris gelatin tipe I, kolagen tipe IV, V, VII dan peptida mirip kolagen dengan urutan Pro-Gln-Gly-,-Ile-Ala-Gly-Gln.[3] Mutasi pada gen MMP2 dapat mengakibatkan sindrom Winchester dan sindrom NAO. Aktivitas MMP-2 terhambat oleh matlistatin A,[4] dan matlistatin B.[5] ...
Neutrophil collagenase, also known as matrix metalloproteinase-8 (MMP-8) or PMNL collagenase (MNL-CL), is a collagen cleaving enzyme which is present in the connective tissue of most mammals. In humans, the MMP-8 protein is encoded by the MMP8 gene. Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is stored in secondary granules within neutrophils and is activated by autolytic cleavage. Its function is degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. GRCh38: Ensembl release 89: ...
ADAM-like, decysin 1 is a protein that in humans is encoded by the ADAMDEC1 gene. This encoded protein is thought to be a secreted protein belonging to the disintegrin metalloproteinase family. Its expression is upregulated during the maturation of dendritic cells. This protein may play an important role in dendritic cell function and their interactions with germinal center T cells. [provided by RefSeq, Jul 2008]. "Entrez Gene: ADAM-like, decysin 1". Retrieved 2014-08-16. Mueller, C. G.; Rissoan, M. C.; Salinas, B; Ait-Yahia, S; Ravel, O; Bridon, J. M.; Briere, F; Lebecque, S; Liu, Y. J. (1997). "Polymerase chain reaction selects a novel disintegrin proteinase from CD40-activated germinal center dendritic cells". The Journal of Experimental Medicine. 186 (5): 655-63. doi:10.1084/jem.186.5.655. PMC 2199019 . PMID 9271581. Bates, E. E.; Fridman, W. H.; Mueller, C. G. (2002). "The ADAMDEC1 (decysin) gene structure: Evolution by duplication in a metalloprotease gene cluster on ...
A disintegrin and metalloproteinase with thrombospondin motifs 8 is an enzyme that in humans is encoded by the ADAMTS8 gene. This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains two C-terminal TS motifs, and disrupts angiogenesis in vivo. A number of disorders have been mapped in the vicinity of this gene, most notably lung neoplasms. GRCh38: Ensembl release 89: ENSG00000134917 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000031994 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Vazquez F, Hastings G, Ortega ...
Metalloendopeptidase OMA1, mitochondrial is an enzyme that in humans is encoded by the OMA1 gene. As a metalloprotease, this protein is a substantial component of the quality control system in the inner membrane of mitochondria. Being activated by enzyme Bax and Bak, mitochondrial protease OMA1 promotes cytochrome c release which subsequently induces apoptosis. The gene OMA1 encodes a metalloprotease, a founding member of a conserved family of membrane-embedded metallopeptidases in mitochondria. The human gene has 9 exons and locates at chromosome band 1p32.2-p32.1 The human protein metalloendopetidase OMA1, mitochondrial is 60.1 kDa in size and composed of 524 amino acids with mitochondrial transition peptide (position 1-13). The mature protein has a theoretical pI of 8.44. The inner membrane of mitochondrial houses two AAA proteases and these membrane-embedded peptidases were termed m- and i-AAA proteases to indicate their ...
Gorbea, C.M., Marchand, P., Jiang, W., Copeland, N.G., Gilbert, D.J., Jenkins, N.A. and Bond, J.S. (1993). "Cloning, expression, and chromosomal localization of the mouse meprin β subunit". J. Biol. Chem. 268: 21035-21043. PMID 8407940. ...
The MMPs are inhibited by specific endogenous tissue inhibitor of metalloproteinases (TIMPs), which comprise a family of four ... Matrix metalloproteinases combines with the metal binding protein, metallothionine; thus helping in metal binding mechanism. ... Proteases in angiogenesis Drug discovery and development of MMP inhibitors Verma RP, Hansch C (March 2007). "Matrix ... This determines substrate specificity and is the site for interaction with TIMPs (tissue inhibitor of metalloproteinases). The ...
Binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent manner. Induces a cascade of intracellular ... Involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from ... The shedding is inhibited by the tissue inhibitor of metalloproteinase TIMP3, and thus probably induced by membrane-bound ... This cleavage is dependent on protein kinase C and tyrosine kinases and can be blocked by protease inhibitors. ...
Kinetic analysis of the binding of human matrix metalloproteinase-2 and -9 to tissue inhibitor of metalloproteinase (TIMP)-1 ... may compete for binding of the protease to αvβ3. Finally, the effects of MMP-2 binding to αvβ3 on signal transduction from this ... Identification of the tissue inhibitor of metalloproteinases-2 (TIMP-2) binding site on the hemopexin carboxyl domain of human ... Intact vitronectin induces matrix metalloproteinase-2 and tissue inhibitor of metalloproteinases-2 expression and enhanced ...
The shedding is inhibited by the tissue inhibitor of metalloproteinase TIMP3, and thus probably induced by membrane-bound ... This cleavage is dependent on protein kinase C and tyrosine kinases and can be blocked by protease inhibitors. ... Cell and tissue imaging tools. Cellular and biochemical assays. By product type. Proteins and Peptides. Proteomics tools. ... Agonists, activators, antagonists and inhibitors. Lysates. Multiplex miRNA assays. By research area. Cancer. Cardiovascular. ...
... because it is inhibited by TNF-α protease inhibitor-2 (TAPI-2) and tissue inhibitor of metalloproteinase-3 (TIMP-3), but not ... Shedding of growth hormone-binding protein is inhibited by hydroxamic acid-based protease inhibitors: proposed mechanism of ... MMP-2, and the colocalized metalloproteinase inhibitor, tissue inhibitor of metalloproteinase-4 (TIMP-4), are released from ... Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry ...
By blocking TSP1 from binding to its cell surface receptor (CD47) normal tissue becomes nearly immune to cancer radiation ... It also interacts with numerous proteases involved in angiogenesis, including plasminogen, urokinase, matrix metalloproteinase ... It is a multi-domain matrix glycoprotein that has been shown to be a natural inhibitor of neovascularization and tumorigenesis ... Bound protein fragments of the type I repeats have been shown to serve as attachment factors for both ECs and melanoma cells. ...
... bind and activate proMMP-9 and to make MMP-9 much less sensitive to inhibition by tissue inhibitors of metalloproteinases and ... causes the protease to remain active in the presence of normally inhibitory amounts of tissue inhibitors of metalloproteinase 1 ... Three small integrin binding ligand N-linked glycoproteins (SIBLINGs) bind and activate specific matrix metalloproteinases. ... Protease-inhibitor systems. Introduction. Dentin matrix protein 1 (DMP1) is an acidic phosphoglycoprotein and member of the ...
Membrane-bound matrix metalloproteinase-8 on activated polymorphonuclear cells is a potent, tissue inhibitor of ... Proteases and protease inhibitors form an important class of MMP substrates. Through zymogen activation and inhibitor ... Identification of the extracellular matrix (ECM) binding motifs of tissue inhibitor of metalloproteinases (TIMP)-3 and ... tissue inhibitor of metalloproteinase. The matrixins or matrix metalloproteinases (MMPs) are members of the large metzincin ...
2013 Mar 15;517(1):12-8. doi: 10.1016/j.gene.2013.01.001. Epub 2013 Jan 11. Comparative Study; Research Support, N.I.H., ... tissue inhibitor of metalloproteinase 3 (TIMP-3) induction. Inhibition of individual signaling pathways revealed that ERK1/2 ... A binding reaction using unlabeled (cold) Sp1 probe was set up for each EMSA assay to demonstrate binding specificity. The Sp1- ... catabolic protease expression, and induction of pro-inflammatory mediators. LfcinB specifically activates ERK1/2, p38 and Akt, ...
... and are modulated by different tissue inhibitors of matrix metalloproteinases.29,48 Although many ADAMs have a relatively well- ... H oxidase and to identify the protease responsible for pro-HB-EGF cleavage. The major matrix-bound metalloproteinases (MMP) and ... but not by CRM197 that causes downregulation of pro-HB-EGF or by the metalloproteinase inhibitor (putative ADAM-12 inhibitor) ... Inhibitors of metalloproteinases (BiPS, KB-R7785) also blocked adrenergic growth. The neutralizing antibody against HB-EGF had ...
... their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP ... MMP-9 and uPA system between colon and rectal cancer tissues. Cancer tissue samples were obtained from colon carcinoma (n = 12 ... The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically ... and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. These ...
Stromal myofibroblasts produce angiogenic factors, proteases, growth factors, immune response-modulating proteins, anti- ... Stromal myofibroblasts produce angiogenic factors, proteases, growth factors, immune response-modulating proteins, anti- ... and tissue inhibitor of metalloproteinase-2 expression and synthetic matrix metalloproteinase-2 inhibitor binding in ovarian ... Cathepsin B, a cysteine protease, and the cysteine protease inhibitor cystatin C were detected in OC cells and their stroma, ...
The most recently discovered group comprise four membrane bound matrix metalloproteinases (MMP-14 to MMP-17) called membrane- ... glycerin containing a cocktail of the following protease inhibitors: 1 mM sodium orthovanadate, 1 mM dithiothreitol, 10 kIU/ml ... 1998) Quantification of matrix metalloproteinases and tissue inhibitors of metalloproteinase in prostatic tissue: analytical ... matrix metalloproteinase. MT-MMP. membrane-type MMP. TIMP. tissue inhibitor of matrix metalloproteinases. PCR. polymerase chain ...
tissue inhibitor of metalloproteinase 2;. bFGF,. basic fibroblast growth factor;. I.U.,. infectious units;. GFP,. green ... Matrix Metalloproteinase 2-Integrin {alpha}v{beta}3 Binding Is Required for Mesenchymal Cell Invasive Activity but Not ... MMP-2 lacks a serine protease recognition motif (10) and is activated at the cell surface of invasive cells by a multimeric ... Matrix Metalloproteinase-9 Is Required for Adequate Angiogenic Revascularization of Ischemic Tissues: Potential Role in ...
It also interacts with many proteases involved in angiogenesis, including plasminogen, urokinase, matrix metalloproteinases, ... matrix glycoprotein that has been shown to be a natural inhibitor of neovascularization and tumorigenesis in healthy tissues. ... It is one of five TSP proteins that have been described to date with almost universal heparin binding capacity (TSP5 is an ... Thrombospondin-1 binds to the reelin receptors Apo ER2 and VLDLR, thereby affecting neuron migration in nasal migration flow. ...
Identification of the tissue inhibitor of metalloproteinases-2 (TIMP-2) binding site on the hemopexin carboxyl domain of human ... Proteases and protease inhibitors in tumor progression Adv Exp Med Biol. 1997; 425:89-97. . View in PubMed ... The C-terminal domain of tissue inhibitor of metalloproteinases-2 is required for cell binding but not for ... Effect of tissue inhibitor of the matrix metalloproteinases-2 expression on the growth and spontaneous metastasis of a human ...
Molecular Function: metalloendopeptidase inhibitor activity; protein binding; protease binding; metal ion binding. Biological ... metalloproteinase inhibitor 3; TIMP-3; MIG-5 protein; protein MIG-5; tissue inhibitor of metalloproteinases 3 ... Embryonic Tissue Antibodies. >29 publications with TIMP3 and Embryonic Tissue. Bone Antibodies. >27 publications with TIMP3 and ... Belongs to the protease inhibitor I35 (TIMP) family.. Protein type: Motility/polarity/chemotaxis; Secreted; Secreted, signal ...
Metalloproteinase inhibitor 3; Tissue inhibitor of metalloproteinases 3; TIMP-3; Protein MIG-5; TIMP3 ... It forms complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their ... the proliferation of quiescent tissues in response to angiogenic factors and by inhibiting protease activity in tissues ... TIMP-3 (Tissue inhibitor of metalloproteinases 3) is a secreted extracellular matrix protein, metalloprotease inhibitor. ...
Tissue Inhibitor of Metalloproteinase 3; Tissue inhibitor of metalloproteinases 3; Tissue inhibitor of metalloproteinases3 ... Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc ... Similarity: Belongs to the protease inhibitor I35 (TIMP) family.. Applications Tested/Suitable for anti-TIMP3 antibody ... Embryonic Tissue Antibodies. >26 publications with TIMP3 and Embryonic Tissue. Bone Antibodies. >24 publications with TIMP3 and ...
Tissue inhibitor of metalloproteinases 2; Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates ... Belongs to the protease inhibitor I35 (TIMP) family. ... them by binding to their catalytic zinc cofactor. Known to act ... on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19; ...
TIMP Metallopeptidase Inhibitor 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - ... Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like ... Gene Ontology (GO) annotations related to this gene include protease binding and metalloendopeptidase inhibitor activity. An ... A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding ...
TIMPs are members of the family of tissue inhibitors of matrix metalloproteinases that include TIMP1, TIMP2, TIMP3, and TIMP4. ... The matrix metalloproteinase (MMP) family of proteases are a group of zinc-dependent enzymes that target extracellular proteins ... SQSTM1/p62-like receptors (SLRs) are a family of autophagy cargo receptors that contain domains for binding to ubiquitin. This ... Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to ...
The shedding is inhibited by the tissue inhibitor of metalloproteinase TIMP3, and thus probably induced by membrane-bound ... This cleavage is dependent on protein kinase C and tyrosine kinases and can be blocked by protease inhibitors. ... Binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent manner. Exhibits a higher affinity for complexes ... Immunohistochemistry: Formalin/PFA-fixed and paraffin-embedded Human liver tissue stained with ARG66630 anti-CD163 antibody [ ...
The Intrinsic Protein Flexibility of Endogenous Protease Inhibitor TIMP-1 Controls Its Binding Interface and Affects Its ... The high-resolution X-ray structure of this complex determined at 2 A could not explain the mechanism of enhanced binding and ... A single point mutation at the distal site of the endogenous tissue inhibitor of metalloproteinase 1 (TIMP-1) enables this ... with tissue inhibitor of metalloproteinase-1 (TIMP-1). *DOI: 10.2210/pdb3MA2/pdb ...
Role of matrix metalloproteinase (MMP) 2 and MMP-9 in soft tissue sarcoma. Clinics in orthopedic surgery. 2014;6:443-54 ... Matrix metalloproteinases (MMPs) are well-known proteases associated with the breakdown of the extracellular matrix (ECM) ... In addition, the laminin receptor, insulin-like growth factor binding protein 1, collagen VI, and α1-proteinase inhibitor are ... Assessment of the association of matrix metalloproteinases with myopia, refractive error and ocular biometric measures in an ...
  • The separate roles that the heparin-binding region of TSP1 plays at high versus low concentrations may be in part responsible for regulating the two-faced nature of TSP1 and giving it a reputation of being both a positive and negative regulator of angiogenesis. (wikipedia.org)
  • Angiogenesis is defined as the sprouting of new blood vessels from existing vessels ( 1 , 2 ). (pnas.org)
  • the treatment comprises administration of an angiogenesis inhibitor, for example, a VEGF inhibitor, whereby a decrease in the amount of Choline after treatment is indicative of a positive response. (google.com)
  • Disclosed also is a method for determining effectiveness of an angiogenesis inhibitor in the treatment of cancer. (google.com)
  • Also disclosed are methods of monitoring early treatment response in diseases where an angiogenesis effector, i.e., an inhibitor or promoter of angiogenesis, is employed. (google.com)
  • 3. The method of claim 1 , wherein the angiogenesis effector molecule causes an interruption in an up-regulated intracellular organelle. (google.com)
  • 6. The method of claim 1 , wherein the angiogenesis effector molecule causes an interruption in a function of the Golgi apparatus, lysosomes, endoplasmic reticulum, mitochondrion, nucleus, peroxisomes or combinations thereof. (google.com)
  • 7. The method of claim 1 , wherein the angiogenesis effector stimulates angiogenesis. (google.com)
  • 9. The method of claim 8 , wherein the angiogenesis effector interrupts one or more pathways selected from the group consisting of a growth factor signaling pathway, an integrin/protease pathway, a coagulation/fibrinolysis pathway, and an inflammatory signaling pathway. (google.com)
  • Other angiogenesis inhibitors, including angiostatin and endostatin, have also been tested in clinical trials [ 4 ], without as yet reaching wide marketing approval. (mdpi.com)
  • 1996). Vascularization of tissues like the yolk sac, embryonic brain, kidney, thymus, limb bud and intersomitic vessels are formed by sprouting angiogenesis (Ekblom et al. (justia.com)
  • 1996). This receptor and its ligands, angiopoietin-1 and 2, are involved in angiogenesis and later vascular remodeling (Dumont et al. (justia.com)
  • Although these inhibitors demonstrate different kinase-selectivity information, in order that their particular systems of inhibiting angiogenesis varies, they all talk about significant activity against CDK9. (angiogenesis-blog.com)
  • The syndecan transmembrane proteoglycans play critical regulatory roles in many biological processes, including wound healing, inflammation, neural patterning, and angiogenesis ( 1 , 2 ). (sciencemag.org)
  • DMP1 had no effect on the invasion of the recombinant BSP-responsive cancer cell lines, suggesting that MMP-2 was the rate-limiting protease for those particular cell lines in the modified Boyden chamber assay. (aacrjournals.org)
  • Both autocatalytically derived and recombinant PEX binds integrin αvβ3 and blocks cell surface activation of MMP-2 ( 17 , 18 ) by competing with MMP-2 for binding to integrin αvβ3 ( 17 ). (pnas.org)
  • Indeed, application of the recombinant noncatalytic carboxyl-terminal hemopexin domain of MMP2 (PEX), which mediates MMP2 binding to integrin α v β 3 , has shown antiangiogenic and antitumor activity in vivo ( 6 ), demonstrating the potential utility of such a targeted strategy. (pnas.org)
  • Recombinant fragment within Mouse CD163 aa 1-250. (abcam.cn)
  • First, the design of recombinant forms of proteases can replace defective protease but are limited by the large doses necessary to achieve this effect. (thno.org)
  • Since 1996, we have lived in the era of US Food and Drug Administration−approved intravenous (IV) recombinant tissue plasminogen activator (rtPA). (ajnr.org)
  • In 1996, the US Food and Drug Administration (FDA) approved intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rtPA, alteplase) for the treatment of acute ischemic stroke within 3 hours of onset after reviewing the results of the National Institute of Neurological Disorder and Stroke (NINDS) and rtPA Stroke Study Group trial. (ajnr.org)
  • The functional involvement in MSC migration was assessed using neutralizing anti-MMP-2 antibody, MMP-2 short interfering RNA or recombinant tissue inhibitor of metalloproteinase (TIMP-3). (haematologica.org)
  • Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. (abcam.com)
  • Platelet-surface sheddases, particularly of the metalloproteinase-disintegrin (ADAM) family, can be regulated by many of the same mechanisms that control receptor function, such as calmodulin association or activation of signaling pathways. (ahajournals.org)
  • 2-6 Major consequences of signal transduction following engagement of GPVI or GPIb-IX-V include (1) activation of platelet integrins, primarily α IIb β 3 that binds vWF or fibrinogen and mediates platelet aggregation, and (2) activation of pathways leading to metalloproteinase-dependent receptor ectodomain shedding. (ahajournals.org)
  • In this study, we examined the hypothesis that epidermal growth factor receptor (EGFR) transactivation and extracellular regulated kinases (ERK) are involved in α 1 -adrenoceptor-mediated SMC growth. (ahajournals.org)
  • In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. (biomedcentral.com)
  • It seems that activation of pro-uPA mostly occurs after binding to its receptor uPAR (uPA receptor). (biomedcentral.com)
  • It was postulated that association of MMP-2 with this receptor/activator complex occurs in two steps: the C-terminal domain of MMP-2 binds to TIMP2 ( 12 ), which, in turn, associates with the membrane-bound MT1-MMP ( 13 - 15 ). (pnas.org)
  • The receptor can bind to pro-inflammatory ligands, including HMGB1 which is elevated in ALI. (bmj.com)
  • Inflammatory mediators, such as thrombin (acting via protease-activated receptor [PAR]), and leukocyte adhesion increase endothelial cell [Ca 2+ ] i , causing the release of pro-ADAM-10 from calmodulin (CAM) and activation of ADAM-10. (ahajournals.org)
  • As a decoy receptor for Gas6, soluble Mer prevented Gas6-mediated stimulation of membrane-bound Mer. (bloodjournal.org)
  • Unlike most chemokines whose function and expression are specific and centered around their role in leukocyte trafficking, both stromal cell-derived factor 1/CXCL12 and its first identified receptor CXCR4 were found to be expressed in a wide variety of cell types and tissues ( 3 ). (jimmunol.org)
  • Nintedanib is a potent small molecule inhibitor of the receptor tyrosine kinases PDGF receptor, FGF receptor and vascular endothelial growth factor receptor. (ersjournals.com)
  • Nintedanib (international non-proprietary name), formerly known by its development code BIBF 1120, is a small molecule that was originally designed as an ATP-competitive inhibitor of fibroblast growth factor receptor (FGFR)-1 and vascular endothelial growth factor receptor (VEGFR)-2. (ersjournals.com)
  • As nintedanib is also an inhibitor of platelet-derived growth factor receptor (PDGFR)-α and β, it was selected for development as a potential treatment for idiopathic pulmonary fibrosis (IPF). (ersjournals.com)
  • 2. A medication, hormone, or other intercellular messenger that binds and blocks the cellular receptor or target enzyme of another agent. (thefreedictionary.com)
  • In 2001, we demonstrated that TIMP-2 could suppress receptor tyrosine kinase (RTK) signaling independent of metalloproteinase inhibition, and that this activity was unique for TIMP-2, and not observed with other members of the TIMP family. (cancer.gov)
  • VEGF and its receptor Flk-1 are thought to be responsible for both primary vessel formations during vasculogenesis and angiogenic invasion of the developing organs (Flamme et al. (justia.com)
  • Both Flk-1 and Flt-1 (placental growth factor receptor) are expressed exclusively in the endothelial cells (Flamme et al. (justia.com)
  • Dystroglycan is a transmembrane receptor that anchors astrocyte endfeet to the parenchymal BM [13-via high-affinity interactions with laminin 1 and 2. (thefreelibrary.com)
  • We survey that MMP digesting of the lengthy amino-terminal CCL15 and CCL23 chemokines as well as the lengthy carboxyl-terminal CCL16, notably with the monocyte/macrophage particular MMP-12, leads to elevated receptor activation or GAG binding, respectively. (colinsbraincancer.com)
  • The separated peptides were tested for opioid-like activity by competitive binding to opioid receptor sites in rat brain tissue in the presence of tritium-labeled dihydromorphine. (blogspot.com)
  • Gene Ontology (GO) annotations related to this gene include protease binding and metalloendopeptidase inhibitor activity . (genecards.org)
  • Second, gene-therapy approaches targeting protease genes can intrinsically improve proper protease activity. (thno.org)
  • The PAI-1 gene is SERPINE1 , located on chromosome 7 (7q21.3-q22). (wikidoc.org)
  • The biological function of myostatin became evident when mice homozygous for a deletion of myostatin gene exhibited a dramatic increase in skeletal muscle mass, with individual muscle groups enlarging to approximately twice their normal size [ 1 ]. (e-jbm.org)
  • In this scenario, PAI-1 inhibits uPA via active site binding, preventing the formation of plasmin. (wikidoc.org)
  • Plasmin also activates latent procollagenases, and hence it has been thought that the plasminogen activator activity of Pla might enhance the invasiveness of Y. pestis by causing damage to host tissue barriers. (asm.org)
  • The neutralizing antibody against HB-EGF had no effect on the two-fold increase in ROS generation induced by phenylephrine (DCF fluorescence), suggesting that stimulation of NAD(P)H oxidase by α 1 -adrenoceptor occupation precedes HB-EGF release. (ahajournals.org)
  • It was suggested that BSP-mediated conformational changes upon partnering with proMMP-2 may facilitate removal of the inhibitory pro-peptide by another protease, which is similar to the binding and activation of proMMP-2 by MT1-MMP. (biomedcentral.com)
  • Tiplaxtinin (PAI-039) is a small molecule inhibitor that is being studied for use in the attenuation of remodeling of blood vessels, a result of arterial hypertension and activation of the renin-angiotensin system . (wikidoc.org)