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.Matrix Metalloproteinase Inhibitors: Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.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.Matrix Metalloproteinase 1: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving FIBRILLAR COLLAGEN. It can degrade interstitial collagens, types I, II and III.Matrix 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.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.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 7: The smallest member of the MATRIX METALLOPROTEINASES. It plays a role in tumor progression.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.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.Tissue Inhibitor of Metalloproteinase-2: A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a 21-kDa nonglycosylated protein found in tissue fluid and is secreted as a complex with progelatinase A by human fibroblast and uncomplexed from alveolar macrophages. An overexpression of TIMP-2 has been shown to inhibit invasive and metastatic activity of tumor cells and decrease tumor growth in vivo.Matrix Metalloproteinase 8: A member of the MATRIX METALLOPROTEINASES that cleaves triple-helical COLLAGEN types I, II, and III.Matrix Metalloproteinase 12: A secreted matrix metalloproteinase which is highly expressed by MACROPHAGES where it may play a role in INFLAMMATION and WOUND HEALING.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.Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-.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.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.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.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.Metalloproteases: Proteases which use a metal, normally ZINC, in the catalytic mechanism. This group of enzymes is inactivated by metal CHELATORS.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Matrix Metalloproteinase 15: A transmembrane domain-containing matrix metalloproteinase that plays a role in the cleavage of proteins in the pericellular environment. It is synthesized as an inactive zymogen that is activated by the action of ENDOPEPTIDASES such as MATRIX METALLOPROTEINASE 14.Matrix Metalloproteinases, Secreted: A subclass of matrix metalloproteinases that are secreted into the pericellular space.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.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).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).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 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.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.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.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.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.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.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.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.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.Gelatin: A product formed from skin, white connective tissue, or bone COLLAGEN. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.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.Phenylmercuric Acetate: A phenyl mercury compound used mainly as a fungicide. Has also been used as a herbicide, slimicide, and bacteriocide.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.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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cell Line, Tumor: A cell line derived from cultured tumor cells.Chondrocytes: Polymorphic cells that form cartilage.Dipeptides: Peptides composed of two amino acid units.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.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.HemopexinThiophenesMolecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes SYNOVIAL FLUID.Nuclear Matrix: The residual framework structure of the CELL NUCLEUS that maintains many of the overall architectural features of the cell nucleus including the nuclear lamina with NUCLEAR PORE complex structures, residual CELL NUCLEOLI and an extensive fibrogranular structure in the nuclear interior. (Advan. Enzyme Regul. 2002; 42:39-52)Proteoglycans: Glycoproteins which have a very high polysaccharide content.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.Hydroxamic Acids: A class of weak acids with the general formula R-CONHOH.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.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.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.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.Doxycycline: A synthetic tetracycline derivative with similar antimicrobial activity.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 184.108.40.206.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.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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cartilage: 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.Mice, Inbred C57BLLaminin: 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.Bone Matrix: Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.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).Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.ElastinPhenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.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.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.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 220.127.116.11.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.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.Collagen Type II: A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.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.Wound Healing: Restoration of integrity to traumatized tissue.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.Interleukin-1beta: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Organic Chemicals: A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form.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.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.Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.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.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.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.Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.Vascular Endothelial Growth Factor A: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.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.)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.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)Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.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.Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.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.Transcription Factor AP-1: A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.GPI-Linked Proteins: A subclass of lipid-linked proteins that contain a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE which holds them to the CELL MEMBRANE.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.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.Synovial Fluid: The clear, viscous fluid secreted by the SYNOVIAL MEMBRANE. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints.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.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Fibrillar Collagens: A family of structurally related collagens that form the characteristic collagen fibril bundles seen in CONNECTIVE TISSUE.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.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.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.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.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.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.Cell Adhesion: Adherence of cells to surfaces or to other cells.Dermis: A layer of vascularized connective tissue underneath the EPIDERMIS. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are SWEAT GLANDS; HAIR FOLLICLES; and SEBACEOUS GLANDS.Trophoblasts: Cells lining the outside of the BLASTOCYST. After binding to the ENDOMETRIUM, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (PLACENTA).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.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.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 18.104.22.168.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Receptors, Mitogen: Glycoprotein molecules on the surface of B- and T-lymphocytes, that react with molecules of antilymphocyte sera, lectins, and other agents which induce blast transformation of lymphocytes.Benzyl CompoundsDNA 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.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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.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.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Chondrosarcoma: A slowly growing malignant neoplasm derived from cartilage cells, occurring most frequently in pelvic bones or near the ends of long bones, in middle-aged and old people. Most chondrosarcomas arise de novo, but some may develop in a preexisting benign cartilaginous lesion or in patients with ENCHONDROMATOSIS. (Stedman, 25th ed)Real-Time Polymerase Chain Reaction: Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.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.Breast Neoplasms: Tumors or cancer of the human BREAST.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.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.Organ Culture Techniques: A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.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.Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.Antigens, CD29: Integrin beta-1 chains which are expressed as heterodimers that are noncovalently associated with specific alpha-chains of the CD49 family (CD49a-f). CD29 is expressed on resting and activated leukocytes and is a marker for all of the very late activation antigens on cells. (from: Barclay et al., The Leukocyte Antigen FactsBook, 1993, p164)Integrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.Connective Tissue: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Stress, Mechanical: A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.Coculture Techniques: A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Tetracyclines: Closely congeneric derivatives of the polycyclic naphthacenecarboxamide. (Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1117)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)Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Oligopeptides: Peptides composed of between two and twelve amino acids.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Myocytes, Smooth Muscle: Non-striated, elongated, spindle-shaped cells found lining the digestive tract, uterus, and blood vessels. They are derived from specialized myoblasts (MYOBLASTS, SMOOTH MUSCLE).Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.Hyaluronic Acid: A natural high-viscosity mucopolysaccharide with alternating beta (1-3) glucuronide and beta (1-4) glucosaminidic bonds. It is found in the UMBILICAL CORD, in VITREOUS BODY and in SYNOVIAL FLUID. A high urinary level is found in PROGERIA.Lung Neoplasms: Tumors or cancer of the LUNG.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Tissue Culture Techniques: A technique for maintaining or growing TISSUE in vitro, usually by DIFFUSION, perifusion, or PERFUSION. The tissue is cultured directly after removal from the host without being dispersed for cell culture.Aorta: The main trunk of the systemic arteries.Antisense Elements (Genetics): Nucleic acids which hybridize to complementary sequences in other target nucleic acids causing the function of the latter to be affected.Cell Culture Techniques: Methods for maintaining or growing CELLS in vitro.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.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.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Astacin: In molecular biology, astacin is a family of metallopeptidases. These metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12A (astacin family, clan MA(M)).Extracellular matrixBasigin: Basigin (BSG) also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147) is a protein that in humans is encoded by the BSG gene. This protein is a determinant for the Ok blood group system.Testican: Testican is a type of proteoglycan. Testican-1 is a highly conserved, multidomain proteoglycan that is most prominently expressed in the thalamus of the brain, and is upregulated in activated astroglial cells of the cerebrum.CollagenPUR4: pUR4 is a recombinant peptide that is known to inhibit the polymerization of fibronectin in a number of cell types including fibroblasts and endothelial cells. Fibronectin is an essential component of the extracellular matrix that acts as a mediator between the extracellular matrix and the cells that reside within the matrix.Zymogen: A zymogen (or proenzyme) is an inactive enzyme precursor. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the active site) for it to become an active enzyme.Mature messenger RNA: Mature messenger RNA, often abbreviated as mature mRNA is a eukaryotic RNA transcript that has been spliced and processed and is ready for translation in the course of protein synthesis. Unlike the eukaryotic RNA immediately after transcription known as precursor messenger RNA, it consists exclusively of exons, with all introns removed.Haptotaxis: Haptotaxis (from Greek ἅπτω (hapto, "touch, fasten") and τάξις (taxis, "arrangement, order")) is the directional motility or outgrowth of cells, e.g.John Adams II: John Adams (July 4, 1803 – October 23, 1834) was the second son of President John Quincy Adams and Louisa Adams. He is usually called John Adams II to distinguish him from President John Adams, his famous grandfather.Gelatin silver process: The gelatin silver process is the photographic process used with currently available black-and-white films and printing papers. This is one of the many ways of producing a photograph.Dermal fibroblast: Dermal fibroblasts are cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles (particularly the rough endoplasmic reticulum), dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers.N-terminal telopeptide: In bone physiology, the N-terminal telopeptide (or more formally, amino-terminal collagen crosslinks, and known by the acronym NTX) is a [that can be used as a biomarker] to measure the rate of [[bone turnover. NTX can be measured in the urine (uNTX) or serum (serum NTX).ChondrocyteDipeptide: A dipeptide is a sometimes ambiguous designation of two classes of organic compounds: Its molecules contain either two amino acids joined by a single peptide bond or one amino acid with two peptide bonds.Articular cartilage repair: The aim of an articular cartilage repair treatment is to restore the surface of an articular joint's hyaline cartilage. Over the last decades, surgeons and researchers have been working hard to elaborate surgical cartilage repair interventions.Hemopexin: Hemopexin (or haemopexin; HPX), also known as beta-1B-glycoprotein is a protein that in humans is encoded by the HPX gene and belongs to hemopexin family of proteins.Benzo(c)thiopheneColes PhillipsFibroblast-like synoviocyte: Fibroblast-like synoviocytes (FLS) represent a specialised cell type located inside joints in the synovium. These cells play a crucial role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis.Nuclear matrix: In biology, the nuclear matrix is the network of fibres found throughout the inside of a cell nucleus and is somewhat analogous to the cell cytoskeleton. However, in contrast to the cytoskeleton, the nuclear matrix has been proposed to be a highly dynamic structure, perhaps more like a dynamic sponge with open compartments for free diffusion of molecules in the nucleus.Proteoglycan: Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s).Osteoarthritis Research Society International: The Osteoarthritis Research Society International (OARSI) is a non-profit scientific organization.OARSI.Hydroxamic acidGross pathology: Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.Protein primary structure: The primary structure of a peptide or protein is the linear sequence of its amino acid structural units, and partly comprises its overall biomolecular structure. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end.Fibronectin: Fibronectin is a high-molecular weight (~440kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Similar to integrins, fibronectin binds extracellular matrix components such as collagen, fibrin, and heparan sulfate proteoglycans (e.DoxycyclineLaminin: Laminins are high-molecular weight (~400kDa) proteins of the extracellular matrix. They are a major component of the basal lamina (one of the layers of the basement membrane), a protein network foundation for most cells and organs.Constitutive enzyme: Constitutive enzymeshttp://goldbook.iupac.Elastin: Elastin is a highly elastic protein in connective tissue and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched.Phenylalanine N-monooxygenase: Phenylalanine N-monooxygenase (, phenylalanine N-hydroxylase, CYP79A2) is an enzyme with system name L-phenylalanine,NADPH:oxygen oxidoreductase (N-hydroxylating). This enzyme catalyses the following chemical reactionRNA transfection: RNA transfection is the process of deliberately introducing RNA into a living cell. RNA can be purified from cells after lysis or synthesized from free nucleotides either chemically, or enzymatically using an RNA polymerase to transcribe a DNA template.Motoko Sasaki filmography: This page contains the filmography of the Japanese pink film actress Motoko Sasaki.Temporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingAngiostasis: Angiostasis is the strict regulation by the body over creation of new blood vessels, which is the normal state (homeostasis) for adult humans. The opposite state of angiostasis is angiogenesis, or the state of generating new blood vessels, as happens after injury, and during tumor growth.UrokinaseSymmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.Eva Engvall: Eva Engvall, born 1940, is one of the scientists who invented ELISA in 1971.Eva Engvall, The Scientist 1995, 9(18):8Wound healing: Wound healing is an intricate process where the skin or other body tissue repairs itself after injury. In normal skin, the epidermis (surface layer) and dermis (deeper layer) form a protective barrier against the external environment.G-CSF factor stem-loop destabilising elementConcentration effect: In the study of inhaled anesthetics, the concentration effect is the increase in the rate that the Fa(alveolar concentration)/Fi(inspired concentration) ratio rises as the alveolar concentration of that gas is increased. In simple terms, the higher the concentration of gas administered, the faster the alveolar concentration of that gas approaches the inspired concentration.
(1/232) Macrophage metalloelastase, MMP-12, cleaves human apolipoprotein(a) in the linker region between kringles IV-4 and IV-5. Potential relevance to lipoprotein(a) biology.
In this study we found that macrophage metalloelastase, MMP-12 cleaves, in vitro, apolipoprotein(a) (apo(a)) in the Asn3518-Val3519 bond located in the linker region between kringles IV-4 and IV-5, a bond immediately upstream of the Ile3520-Leu3521 bond, shown previously to be the site of action by neutrophil elastase (NE). We have also shown that human apo(a) injected into the tail vein of control mice undergoes degradation as reflected by the appearance of immunoreactive fragments in the plasma and in the urine of these animals. To define whether either or both of these enzymes may be responsible for the in vivo apo(a) cleavage, we injected intravenously MMP-12(-/-), NE -/- mice and litter mates, all of the same strain, with either lipoprotein(a) (Lp(a)), full-length free apo(a), or its N-terminal fragment, F1, obtained by the in vitro cleavage of apo(a) by NE. In the plasma of Lp(a)/apo(a)-injected mice, F1 was detected in control and NE -/- mice but was virtually absent in the MMP-12(-/-) mice. Moreover, fragments of the F1 type were present in the urine of the animals except for the MMP-12(-/-) mice. These fragments were significantly smaller in size than those observed in the plasma. All of the animals injected with F1 exhibited small sized fragments in their urine. These observations provide evidence that, in the mouse strain used, MMP-12 plays an important role in the generation of F1 from injected human Lp(a)/apo(a) and that this fragment undergoes further cleavage during renal transit via a mechanism that is neither NE- nor MMP-12-dependent. Thus, factors influencing the expression of MMP-12 may have a modulating action on the biology of Lp(a). (+info)
(2/232) Enhanced expression of human metalloelastase (MMP-12) in cutaneous granulomas and macrophage migration.
Accumulation of inflammatory cells such as macrophages may lead to degeneration of connective tissue matrix in various skin diseases. Macrophage metalloelastase, is a matrix metalloproteinase (MMP-12) capable of degrading elastin as well as various basement membrane components. To investigate the role of human macrophage metalloelastase in skin, we assessed by in situ hybridization and immunohistochemistry 66 specimens representing skin diseases characterized either by changes in elastic fibers or by pronounced infiltrations of extravasating and migrating macrophages. CD68 immunostaining was performed to identify the human macrophage metalloelastase-positive cells and Weigert's Resorcin-Fuchsin staining to reveal the status of elastic fibers. We found abundant expression of human macrophage metalloelastase mRNA in macrophages in areas devoid of normal elastic fibers in granulomatous skin diseases sarcoidosis, necrobiosis lipoidica diabeticorum, and granuloma annulare. Positive cells for human macrophage metalloelastase protein could be detected in the same regions as well as positive immunostaining for urokinase plasminogen activator. Of the other matrix metalloproteinases capable of degrading elastin, 92 kDa gelatinase colocalized with human macrophage metalloelastase, while 72 kDa gelatinase was produced by surrounding fibroblast-like cells. Furthermore, human macrophage metalloelastase was expressed by macrophages in areas with disrupted basement membrane, as assessed by type IV collagen staining, in pityriasis lichenoides and dermatitis herpetiformis. Specimens of anetoderma, acrodermatitis chronica atrophicans and pseudoxanthoma elasticum showed no signal for human macrophage metalloelastase. Matrilysin was not detected in any of the samples investigated. Our study suggests that human macrophage metalloelastase may contribute to elastin degradation occurring in granulomatous skin diseases and may aid macrophage migration through the epidermal and vascular basement membranes in inflammatory disorders. (+info)
(3/232) Induction and regulation of macrophage metalloelastase by hyaluronan fragments in mouse macrophages.
Although the metalloproteinase murine metalloelastase (MME) has been implicated in lung disorders such as emphysema and pulmonary fibrosis, the mechanisms regulating MME expression are unclear. Low m.w. fragments of the extracellular matrix component hyaluronan (HA) that accumulate at sites of lung inflammation are capable of inducing inflammatory gene expression in macrophages (Mphi). The purpose of this study was to examine the effect of HA fragments on the expression of MME in alveolar Mphi. The mouse alveolar Mphi cell line MH-S was stimulated with HA fragments over time, total RNA was isolated, and Northern blot analysis was performed. HA fragments induced MME mRNA in a time-dependent fashion, with maximal levels at 6 h. HA fragments also induced MME protein expression as well as enzyme activity. The induction of MME gene expression was specific for low m.w. HA fragments and dependent upon new protein synthesis; it occurred at the level of gene transcription. We also examined the effect of HA fragments on MME expression in inflammatory alveolar Mphi from bleomycin-injured rat lungs. Although normal rat alveolar Mphi did not express MME mRNA in response to HA fragments, alveolar Mphi from the bleomycin-treated rats responded to HA fragment stimulation by increasing MME mRNA levels. Furthermore, baseline and HA fragment-induced MME gene expression in alveolar Mphi from bleomycin-treated rats was inhibited by IFN-gamma. These data suggest that HA fragments may be an important mechanism for the expression of MME by Mphi in inflammatory lung disorders. (+info)
(4/232) Induction of metalloelastase mRNA in murine peritoneal macrophages by diethylmaleate.
Macrophage-specific metalloelastase (MME) hydrolyzes elastin and other matrix proteins and plays an important physiological role in tissue remodeling and pathological tissue destruction. We have examined the effects of diethylmaleate (DEM), an electrophilic agent that reacts with sulfhydryls, on the expression of MME mRNA in mouse peritoneal macrophages. Quantification of MME mRNA by Northern blot analysis revealed that basal mRNA levels were quite low in freshly isolated cells, although mRNA levels increased markedly and reached a steady level within 12 h when cells were cultured in a serum-supplemented RPMI 1640 medium. When macrophages were challenged with DEM at 0.05-1.0 mM for 8 h the expression of the MME gene was enhanced further. In the presence of 0.1 mM DEM, the level of the MME mRNA increased 2-fold compared to the control levels after 6-9 h and decreased to control levels in 24 h. Other electrophilic agents, catechol and 1-chloro-2,4-dinitrobenzene, also enhanced MME gene expression. However, oxidative stress agents such as hydrogen peroxide, menadione, paraquat (an O-2 generator), sodium arsenite and cadmium chloride had no effect on MME gene expression. These results indicate that the electrophilic agents selectively enhance the expression of MME mRNA during primary culture of the macrophages. (+info)
(5/232) CA-MMP: a matrix metalloproteinase with a novel cysteine array, but without the classic cysteine switch.
A matrix metalloproteinase (MMP)-like gene was identified in mouse to contain a conserved MMP catalytic domain and an RRRR motif. It lacks a classic cysteine switch, but it possesses two novel motifs: a cysteine array (Cys-X(6)-Cys-X(8)-Cys-X(10)-Cys-X(3)-Cys-X(2)-Cys), and a novel Ig-fold. It is named CA-MMP after the distinct cysteine array motif, and little is known about its biochemical function. In an attempt to characterize CA-MMP activity, the full-length sequence was expressed in mammalian cells and its product found to be cell-associated without detectable secretion. In light of this unusual finding, a chimera combining the catalytic domain of CA-MMP with the prodomain of stromelysin-3 was constructed to express a fully active enzyme in mammalian cells. Purified CA-MMP catalytic domain expresses proteolytic activity against protein substrates in an MMP inhibitor sensitive fashion. Taken together, it is concluded that CA-MMP is an MMP with distinct structure, biochemical properties and evolutionary history that may define a new subclass of the MMP superfamily. (+info)
(6/232) Monocyte inflammation augments acrolein-induced Muc5ac expression in mouse lung.
Acrolein, an unsaturated aldehyde found in smog and tobacco smoke, can induce airway hyperreactivity, inflammation, and mucus hypersecretion. To determine whether changes in steady-state mucin gene expression (Muc2 and Muc5ac) are associated with inflammatory cell accumulation and neutrophil elastase activity, FVB/N mice were exposed to acrolein (3.0 parts/million; 6 h/day, 5 days/wk for 3 wk). The levels of Muc2 and Muc5ac mRNA were determined by RT-PCR, and the presence of Muc5ac protein was detected by immunohistochemistry. Total and differential cell counts were determined from bronchoalveolar lavage (BAL) fluid, and neutrophil elastase activity was measured in the BAL fluid supernatant. Lung Muc5ac mRNA was increased on days 12 and 19, and Muc5ac protein was detected in mucous granules and on the surface of the epithelium on day 19. Lung Muc2 mRNA was not detected at measurable levels in either control or exposed mice. Acrolein exposure caused a significant and persistent increase in macrophages and a rapid but transient increase in neutrophils in BAL fluid. Recoverable neutrophil elastase activity was not significantly altered at any time after acrolein exposure. To further examine the role of macrophage accumulation in mucin gene expression, additional strains of mice (including a strain genetically deficient in macrophage metalloelastase) were exposed to acrolein for 3 wk, and Muc5ac mRNA levels and macrophage accumulation were measured. The magnitude of macrophage accumulation coincided with increased Muc5ac mRNA levels, indicating that excessive macrophage accumulation augments acrolein-induced Muc5ac synthesis and secretion after repeated exposure. These findings support a role for chronic monocytic inflammation in the pathogenesis of mucus hypersecretion observed in chronic bronchitis. (+info)
(7/232) Accumulation of matrilysin (MMP-7) and macrophage metalloelastase (MMP-12) in actinic damage.
Photodamage is characterized by degradation of collagen and accumulation of abnormal elastin in the superficial dermis and several matrix metalloproteinases have previously been implicated in this process. Using immunohistochemistry and in situ hybridization, we have studied the localization of two elastolytic matrix metalloproteinases, matrilysin (matrix metalloproteinase-7) and human macrophage metalloelastase (matrix metalloproteinase-12) in solar damage. Human macrophage metalloelastase protein was detected in the superficial dermis in areas of elastotic material. Matrix metalloproteinase-7 was seen in the mid-dermis in regions with less damaged elastic fibers and morphologically better preserved collagen as well as in a band-like pattern below basal keratinocytes in eight of 18 solar elastosis. In samples taken from healthy volunteers 3 d after repeated ultraviolet A or ultraviolet B photoprovocation, occasional immunopositive cells for human macrophage metalloelastase (stromal) or matrix metalloproteinase-7 (sweat gland epithelium) were detected. In samples taken 1 d after ultraviolet B exposure, however, basal keratinocytes were matrix metalloproteinase-7 immunopositive, explaining the linear immunostaining below basal keratinocytes noted particularly in ultraviolet B treated 3 d specimens. Upregulation of metalloelastase was also demonstrated in the skin of hairless mice after repeated ultraviolet exposure. In normal skin, no staining for human macrophage metalloelastase or matrix metalloproteinase-7 was observed in association with elastin. The amount of immunoreactivity for the substrates of matrix metalloproteinase-7, versican, and tenascin, was clearly increased in solar elastosis and photoprovocated skin; versican but not tenascin was detected in the same areas as matrix metalloproteinase-7. Our results suggest that both matrix metalloproteinase-7 and -12 may contribute to remodeling of elastotic areas in sun-damaged skin. (+info)
(8/232) Implications of human macrophage metalloelastase and vascular endothelial growth factor gene expression in angiogenesis of hepatocellular carcinoma.
OBJECTIVE: To determine molecular mechanisms involved in angiogenesis of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Tumor angiogenesis is believed to derive from the balance between angiogenic stimulators and inhibitors. It has been suggested that the switch to the angiogenic phenotype requires both upregulation of the first and downregulation of the second. However, its molecular basis in vivo remains obscure. In this study the authors analyze the participation of two factors in angiogenesis of HCC- human macrophage metalloelastase (HME), a matrix metalloproteinase responsible for the generation of angiostatin, a potent angiogenesis inhibitor, and vascular endothelial growth factor (VEGF), the most potent endogenous angiogenic factor. METHODS: Tumorous and contiguous nontumorous tissues from 25 patients with HCC who underwent curative partial hepatectomy were subjected to Northern blot analysis to detect HME and VEGF messenger RNA (mRNA) expression. Western blot analysis was used to detected angiostatin. Tumor vascularity was evaluated using hepatic angiography. RESULTS: Eleven of the 15 cases expressing the HME gene showed hypovascular tumors, whereas hypervascular tumors were seen in 9 of the 10 HME-negative cases. The median of HME mRNA expression (tumorous/nontumorous ratio) was 6.5 (range 0-264.5) in the hypovascular group and 0 (range 0-3.2) in the hypervascular group. A stepwise logistic analysis revealed that HME and VEGF mRNA expression were two independent variables significantly affecting the vascularity of HCC tumors. CONCLUSION: HME gene expression is significantly associated with hypovascular tumors; moreover, angiogenesis in HCC is not determined by a single factor, but depends on the net balance between HME and VEGF gene expressions. (+info)