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).
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.
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.
Tenascin
Hexameric extracellular matrix glycoprotein transiently expressed in many developing organs and often re-expressed in tumors. It is present in the central and peripheral nervous systems as well as in smooth muscle and tendons. (From Kreis & Vale, Guidebook to the Extracellular Matrix and Adhesion Proteins, 1993, p93)
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.
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).
Cartilage Oligomeric Matrix Protein
Major component of chondrocyte EXTRACELLULAR MATRIX of various tissues including bone, tendon, ligament, SYNOVIUM and blood vessels. It binds MATRILIN PROTEINS and is associated with development of cartilage and bone.
Matrilin Proteins
PROTEOGLYCANS-associated proteins that are major components of EXTRACELLULAR MATRIX of various tissues including CARTILAGE; and INTERVERTEBRAL DISC structures. They bind COLLAGEN fibers and contain protein domains that enable oligomer formation and interaction with other extracellular matrix proteins such as CARTILAGE OLIGOMERIC MATRIX PROTEIN.
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.
Viral Matrix Proteins
Proteins associated with the inner surface of the lipid bilayer of the viral envelope. These proteins have been implicated in control of viral transcription and may possibly serve as the "glue" that binds the nucleocapsid to the appropriate membrane site during viral budding from the host cell.
Cells, Cultured
Matrix Metalloproteinases
A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.
Matrix Metalloproteinase 2
Fibroblasts
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Collagen Type I
Cell Movement
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.
Vitronectin
A blood plasma glycoprotein that mediates cell adhesion and interacts with proteins of the complement, coagulation, and fibrinolytic cascade. (From Segen, Dictionary of Modern Medicine, 1992)
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.
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.
Thrombospondins
A family of related, adhesive glycoproteins which are synthesized, secreted, and incorporated into the extracellular matrix of a variety of cells, including alpha granules of platelets following thrombin activation and endothelial cells. They interact with a number of BLOOD COAGULATION FACTORS and anticoagulant factors. Five distinct forms have been identified, thrombospondin 1, -2, -3, -4, and cartilage oligomeric matrix protein (COMP). They are involved in cell adhesion, platelet aggregation, cell proliferation, angiogenesis, tumor metastasis, VASCULAR SMOOTH MUSCLE growth, and tissue repair.
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.
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)
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.
Glycoproteins
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
Osteonectin
Non-collagenous, calcium-binding glycoprotein of developing bone. It links collagen to mineral in the bone matrix. In the synonym SPARC glycoprotein, the acronym stands for Secreted Protein, Acidic and Rich in Cysteine.
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.
Matrix Metalloproteinase Inhibitors
Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.
Immunohistochemistry
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Elastin
'Elastin' is a highly elastic protein in connective tissue that allows many tissues in the body to resume their shape after stretching or contracting, such as the skin, lungs, and blood vessels.
Dental Enamel Proteins
The proteins that are part of the dental enamel matrix.
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.
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)
Cell Adhesion Molecules, Neuronal
Surface ligands that mediate cell-to-cell adhesion and function in the assembly and interconnection of the vertebrate nervous system. These molecules promote cell adhesion via a homophilic mechanism. These are not to be confused with NEURAL CELL ADHESION MOLECULES, now known to be expressed in a variety of tissues and cell types in addition to nervous tissue.
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.
Chondroitin Sulfate Proteoglycans
Proteoglycans consisting of proteins linked to one or more CHONDROITIN SULFATE-containing oligosaccharide chains.
Bone Matrix
Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.
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.
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.
Cell Adhesion Molecules
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
Osteopontin
A negatively-charged extracellular matrix protein that plays a role in the regulation of BONE metabolism and a variety of other biological functions. Cell signaling by osteopontin may occur through a cell adhesion sequence that recognizes INTEGRIN ALPHA-V BETA-3.
Cell Differentiation
Gene Expression Regulation
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.
Fibrosis
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
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.
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.
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.
Reverse Transcriptase Polymerase Chain Reaction
Fluorescent Antibody Technique
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
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)
Thrombospondin 1
An extracellular matrix glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin. Thrombospondin-1 is believed to play a role in cell migration and proliferation, during embryogenesis and wound repair. Also, it has been studied for its use as a potential regulator of tumor growth and metastasis.
Amelogenin
Receptors, Fibronectin
Specific cell surface receptors which bind to FIBRONECTINS. Studies have shown that these receptors function in certain types of adhesive contact as well as playing a major role in matrix assembly. These receptors include the traditional fibronectin receptor, also called INTEGRIN ALPHA5BETA1 and several other integrins.
Glycosaminoglycans
Base Sequence
Sialoglycoproteins
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.
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.
Calcification, Physiologic
Integrin alpha5
This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.
Tissue Engineering
Biglycan
Receptors, Vitronectin
Receptors such as INTEGRIN ALPHAVBETA3 that bind VITRONECTIN with high affinity and play a role in cell migration. They also bind FIBRINOGEN; VON WILLEBRAND FACTOR; osteopontin; and THROMBOSPONDINS.
Chondrocytes
Polymorphic cells that form cartilage.
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.
Integrin alphaV
An alpha integrin with a molecular weight of 160-kDa that is found in a variety of cell types. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds. Integrin alphaV can combine with several different beta subunits to form heterodimers that generally bind to RGD sequence-containing extracellular matrix proteins.
Cell Division
Chick Embryo
Brevican
Gene Expression
Dystroglycans
Dystrophin-associated proteins that play role in the formation of a transmembrane link between laminin-2 and DYSTROPHIN. Both the alpha and the beta subtypes of dystroglycan originate via POST-TRANSLATIONAL PROTEIN PROCESSING of a single precursor protein.
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.
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.
Mice, Inbred C57BL
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
Collagenases
Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.
Lipoid Proteinosis of Urbach and Wiethe
An autosomal recessive disorder characterized by glassy degenerative thickening (hyalinosis) of SKIN; MUCOSA; and certain VISCERA. This disorder is caused by mutation in the extracellular matrix protein 1 gene (ECM1). Clinical features include hoarseness and skin eruption due to widespread deposition of HYALIN.
Decorin
A small leucine-rich proteoglycan that interacts with FIBRILLAR COLLAGENS and modifies the EXTRACELLULAR MATRIX structure of CONNECTIVE TISSUE. Decorin has also been shown to play additional roles in the regulation of cellular responses to GROWTH FACTORS. The protein contains a single glycosaminoglycan chain and is similar in structure to BIGLYCAN.
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.
Hyaluronic Acid
Integrin alpha6beta1
A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.
Cattle
Connective Tissue Growth Factor
A CCN protein family member that regulates a variety of extracellular functions including CELL ADHESION; CELL MIGRATION; and EXTRACELLULAR MATRIX synthesis. It is found in hypertrophic CHONDROCYTES where it may play a role in CHONDROGENESIS and endochondral ossification.
Cell Proliferation
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
Connective Tissue
Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.
Collagen Type VI
A non-fibrillar collagen that forms a network of MICROFIBRILS within the EXTRACELLULAR MATRIX of CONNECTIVE TISSUE. The alpha subunits of collagen type VI assemble into antiparallel, overlapping dimers which then align to form tetramers.
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.
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.
Skin
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
Cell-Matrix Junctions
Specialized areas at the CELL MEMBRANE where a cell attaches to the EXTRACELLULAR MATRIX or other substratum.
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.
Bacterial Adhesion
Gelatinases
A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-.
Microscopy, Electron
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Heparan Sulfate Proteoglycans
Ubiquitous macromolecules associated with the cell surface and extracellular matrix of a wide range of cells of vertebrate and invertebrate tissues. They are essential cofactors in cell-matrix adhesion processes, in cell-cell recognition systems, and in receptor-growth factor interactions. (From Cancer Metastasis Rev 1996; 15(2): 177-86; Hepatology 1996; 24(3): 524-32)
Glomerular Mesangium
The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX.
Transfection
Actins
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
Focal Adhesion Protein-Tyrosine Kinases
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.
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.
Electrophoresis, Polyacrylamide Gel
Phenotype
Stress, Mechanical
Integrin alphaVbeta3
An integrin that binds to a variety of plasma and extracellular matrix proteins containing the conserved RGD amino acid sequence and modulates cell adhesion. Integrin alphavbeta3 is highly expressed in OSTEOCLASTS where it may play role in BONE RESORPTION. It is also abundant in vascular smooth muscle and endothelial cells, and in some tumor cells, where it is involved in angiogenesis and cell migration. Although often referred to as the vitronectin receptor there is more than one receptor for vitronectin (RECEPTORS, VITRONECTIN).
Nuclear Matrix-Associated Proteins
A broad category of nuclear proteins that are components of or participate in the formation of the NUCLEAR MATRIX.
Procollagen
A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains.
Receptors, Laminin
Glycoprotein molecules on the surface of cells that react with or bind to laminin whose function allows the binding of epithelial cells to the basement membrane. The molecular weight of this high-affinity receptor is 67 kD.
Membrane Proteins
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.
Endothelium, Vascular
Protein-Lysine 6-Oxidase
Microscopy, Fluorescence
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Tropoelastin
A salt-soluble precursor of elastin. Lysyl oxidase is instrumental in converting it to elastin in connective tissue.
Cytoskeleton
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.
In Situ Hybridization
Integrin alpha Chains
The alpha subunits of integrin heterodimers (INTEGRINS), which mediate ligand specificity. There are approximately 18 different alpha chains, exhibiting great sequence diversity; several chains are also spliced into alternative isoforms. They possess a long extracellular portion (1200 amino acids) containing a MIDAS (metal ion-dependent adhesion site) motif, and seven 60-amino acid tandem repeats, the last 4 of which form EF HAND MOTIFS. The intracellular portion is short with the exception of INTEGRIN ALPHA4.
Microfilament Proteins
Binding Sites
Cell Line, Tumor
A cell line derived from cultured tumor cells.
Rats, Sprague-Dawley
Heparin
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
Integrin alpha1
Cysteine-Rich Protein 61
A CCN protein family member that regulates a variety of extracellular functions including CELL ADHESION; CELL MIGRATION; and EXTRACELLULAR MATRIX synthesis. It may play an important role in the development of branched CAPILLARIES during EMBRYOGENESIS.
Peptide Fragments
Blotting, Northern
Microscopy, Electron, Scanning
Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY.
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.
Heparitin Sulfate
A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.
Myofibroblasts
Spindle-shaped cells with characteristic CONTRACTILE PROTEINS and structures that contribute to the WOUND HEALING process. They occur in GRANULATION TISSUE and also in pathological processes such as FIBROSIS.
Disease Models, Animal
Cell Communication
Osteoblasts
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
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.
Latent TGF-beta Binding Proteins
A family of secreted multidomain proteins that were originally identified by their association with the latent form of TRANSFORMING GROWTH FACTORS. They interact with a variety of EXTRACELLULAR MATRIX PROTEINS and may play a role in the regulation of TGB-beta bioavailability.
Biocompatible Materials
Gene Expression Regulation, Developmental
Epithelium
One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.
Gene Expression Profiling
Bone Morphogenetic Protein 5
A bone morphogenetic protein that may play a role in CARTILAGE formation. It is a potent regulator of the growth of CHONDROCYTES and the synthesis of cartilage matrix proteins. Evidence for its role in cartilage formation can be seen in MICE, where genetic mutations that cause loss of bone morphogenetic protein 5 function result in the formation of small malformed ears.
DNA, Complementary
Focal Adhesion Kinase 1
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
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.
Matrix Metalloproteinase 7
The smallest member of the MATRIX METALLOPROTEINASES. It plays a role in tumor progression.
Versicans
HYALURONAN-containing proteoglycans found in the EXTRACELLULAR MATRIX of a variety of tissues and organs. Several versican isoforms exist due to multiple ALTERNATIVE SPLICING of the versican MESSENGER RNA.
Adhesins, Bacterial
Cell-surface components or appendages of bacteria that facilitate adhesion (BACTERIAL ADHESION) to other cells or to inanimate surfaces. Most fimbriae (FIMBRIAE, BACTERIAL) of gram-negative bacteria function as adhesins, but in many cases it is a minor subunit protein at the tip of the fimbriae that is the actual adhesin. In gram-positive bacteria, a protein or polysaccharide surface layer serves as the specific adhesin. What is sometimes called polymeric adhesin (BIOFILMS) is distinct from protein adhesin.
Fibrinogen
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
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.
Elastic Tissue
Connective tissue comprised chiefly of elastic fibers. Elastic fibers have two components: ELASTIN and MICROFIBRILS.
Phosphorylation
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.
Hydrogels
Morphogenesis
The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.
Mesangial Cells
Smooth muscle-like cells adhering to the wall of the small blood vessels of the KIDNEY at the glomerulus and along the vascular pole of the glomerulus in the JUXTAGLOMERULAR APPARATUS. They are myofibroblasts with contractile and phagocytic properties. These cells and their MESANGIAL EXTRACELLULAR MATRIX constitute the GLOMERULAR MESANGIUM.
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.
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.
Kidney
Mutation
Collagen Type II
Tissue Scaffolds
Cell growth support structures composed of BIOCOMPATIBLE MATERIALS. They are specially designed solid support matrices for cell attachment in TISSUE ENGINEERING and GUIDED TISSUE REGENERATION uses.
Lung
Culture Media, Conditioned
Calcium-Binding Proteins
Integrin beta3
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
Antibodies
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
DNA Primers
Cell Membrane
Focal Adhesions
An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of the ACTIN CYTOSKELETON terminate and attach to the transmembrane linkers, INTEGRINS, which in turn attach through their extracellular domains to EXTRACELLULAR MATRIX PROTEINS.
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.
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.
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.
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.
Cloning, Molecular
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.
Keratan Sulfate
A sulfated mucopolysaccharide initially isolated from bovine cornea. At least two types are known. Type I, found mostly in the cornea, contains D-galactose and D-glucosamine-6-O-sulfate as the repeating unit; type II, found in skeletal tissues, contains D-galactose and D-galactosamine-6-O-sulfate as the repeating unit.
Serine Endopeptidases
Integrin alpha3beta1
Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.
Metalloproteases
Growth Substances
Receptors, Cytoadhesin
A group of INTEGRINS that includes the platelet outer membrane glycoprotein GPIIb-IIIa (PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX) and the vitronectin receptor (RECEPTORS, VITRONECTIN). They play a major role in cell adhesion and serve as receptors for fibronectin, von Willebrand factor, and vitronectin.
Cell Survival
Receptors, Cell Surface
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Carrier Proteins
Transport proteins that carry specific substances in the blood or across cell membranes.
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.