Fibrillar Collagens
A family of structurally related collagens that form the characteristic collagen fibril bundles seen in CONNECTIVE TISSUE.
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).
Collagen Type I
Collagen Type V
A fibrillar collagen found widely distributed as a minor component in tissues that contain COLLAGEN TYPE I and COLLAGEN TYPE III. It is a heterotrimeric molecule composed of alpha1(V), alpha2(V) and alpha3(V) subunits. Several forms of collagen type V exist depending upon the composition of the subunits that form the trimer.
Procollagen
A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains.
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.
Receptors, Collagen
Collagen receptors are cell surface receptors that modulate signal transduction between cells and the EXTRACELLULAR MATRIX. They are found in many cell types and are involved in the maintenance and regulation of cell shape and behavior, including PLATELET ACTIVATION and aggregation, through many different signaling pathways and differences in their affinities for collagen isoforms. Collagen receptors include discoidin domain receptors, INTEGRINS, and glycoprotein VI.
Collagen Type XI
A fibrillar collagen found primarily in interstitial CARTILAGE. Collagen type XI is heterotrimer containing alpha1(XI), alpha2(XI) and alpha3(XI) subunits.
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.
Collagen Type II
Integrin alpha2beta1
An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.
Receptors, Mitogen
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.
Bone Morphogenetic Protein 1
A bone morphogenetic protein family member that includes an active tolloid-like metalloproteinase domain. The metalloproteinase activity of bone morphogenetic protein 1 is specific for the removal of the C-propeptide of PROCOLLAGEN and may act as a regulator of EXTRACELLULAR MATRIX deposition. Alternative splicing of MRNA for bone morphogenetic protein 1 results in the production of several PROTEIN ISOFORMS.
Fibroblasts
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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).
Platelet Adhesiveness
The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.
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.
Collagenases
Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.
Microscopy, Polarization
Hydroxyproline
A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.
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.
Matrix Metalloproteinases
A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.
Heart Failure, Diastolic
Cells, Cultured
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.
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.
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.
Tendons
Fibrous bands or cords of CONNECTIVE TISSUE at the ends of SKELETAL MUSCLE FIBERS that serve to attach the MUSCLES to bones and other structures.
Fibrosis
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
Procollagen N-Endopeptidase
An extracellular endopeptidase which excises a block of peptides at the amino terminal, nonhelical region of the procollagen molecule with the formation of collagen. Absence or deficiency of the enzyme causes accumulation of procollagen which results in the inherited connective tissue disorder--dermatosparaxis. EC 3.4.24.14.
Porifera
The phylum of sponges which are sessile, suspension-feeding, multicellular animals that utilize flagellated cells called choanocytes to circulate water. Most are hermaphroditic. They are probably an early evolutionary side branch that gave rise to no other group of animals. Except for about 150 freshwater species, sponges are marine animals. They are a source of ALKALOIDS; STEROLS; and other complex molecules useful in medicine and biological research.
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.
Skin
Corneal Stroma
The lamellated connective tissue constituting the thickest layer of the cornea between the Bowman and Descemet membranes.
Blood Platelets
HSP47 Heat-Shock Proteins
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Connective Tissue
Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.
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.
Ehlers-Danlos Syndrome
A heterogeneous group of autosomally inherited COLLAGEN DISEASES caused by defects in the synthesis or structure of FIBRILLAR COLLAGEN. There are numerous subtypes: classical, hypermobility, vascular, and others. Common clinical features include hyperextensible skin and joints, skin fragility and reduced wound healing capability.
Collagen Diseases
Historically, a heterogeneous group of acute and chronic diseases, including rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, dermatomyositis, etc. This classification was based on the notion that "collagen" was equivalent to "connective tissue", but with the present recognition of the different types of collagen and the aggregates derived from them as distinct entities, the term "collagen diseases" now pertains exclusively to those inherited conditions in which the primary defect is at the gene level and affects collagen biosynthesis, post-translational modification, or extracellular processing directly. (From Cecil Textbook of Medicine, 19th ed, p1494)
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.
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.
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.
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.
von Willebrand Factor
A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor.
Collagen Type XVIII
A non-fibrillar collagen found in BASEMENT MEMBRANE. The C-terminal end of the alpha1 chain of collagen type XVIII contains the ENDOSTATIN peptide, which can be released by proteolytic cleavage.
Base Sequence
Cornea
The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous CORNEAL EPITHELIUM; BOWMAN MEMBRANE; CORNEAL STROMA; DESCEMET MEMBRANE; and mesenchymal CORNEAL ENDOTHELIUM. It serves as the first refracting medium of the eye. It is structurally continuous with the SCLERA, avascular, receiving its nourishment by permeation through spaces between the lamellae, and is innervated by the ophthalmic division of the TRIGEMINAL NERVE via the ciliary nerves and those of the surrounding conjunctiva which together form plexuses. (Cline et al., Dictionary of Visual Science, 4th ed)
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.
Sea Anemones
Cloning, Molecular
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Platelet Aggregation
The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.
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.
Cattle
Immunohistochemistry
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.
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)
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.
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.
Biomechanical Phenomena
Cardiomegaly
Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.
Platelet Membrane Glycoproteins
Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.
Hydroxylysine
Cell Movement
Chick Embryo
Genes
Exons
Gels
Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.
Fibril-Associated Collagens
A family of non-fibrillar collagens that interact with FIBRILLAR COLLAGENS. They contain short triple helical domains interrupted by short non-helical domains and do not form into collagen fibrils.
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.
Collagen Type X
A non-fibrillar collagen found primarily in terminally differentiated hypertrophic CHONDROCYTES. It is a homotrimer of three identical alpha1(X) subunits.
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.
Peptide Fragments
DNA
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Disease Models, Animal
Gene Expression
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
Recombinant Proteins
Proteins prepared by recombinant DNA technology.
Sequence Homology, Nucleic Acid
In Situ Hybridization
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.
Collagen Type XII
Microbial Collagenase
A metalloproteinase which degrades helical regions of native collagen to small fragments. Preferred cleavage is -Gly in the sequence -Pro-Xaa-Gly-Pro-. Six forms (or 2 classes) have been isolated from Clostridium histolyticum that are immunologically cross-reactive but possess different sequences and different specificities. Other variants have been isolated from Bacillus cereus, Empedobacter collagenolyticum, Pseudomonas marinoglutinosa, and species of Vibrio and Streptomyces. EC 3.4.24.3.
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.
Gene Expression Regulation
Vertebrates
Collagen Type VII
A non-fibrillar collagen involved in anchoring the epidermal BASEMENT MEMBRANE to underlying tissue. It is a homotrimer comprised of C-terminal and N-terminal globular domains connected by a central triple-helical region.
DNA, Complementary
Protein Conformation
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Nucleic Acid Hybridization
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
Rats, Sprague-Dawley
Pepsin A
Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice.
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.
Sequence Homology, Amino Acid
Reverse Transcriptase Polymerase Chain Reaction
Cartilage, Articular
A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact.
Non-Fibrillar Collagens
Collagen Type VIII
A non-fibrillar collagen originally found in DESCEMET MEMBRANE. It is expressed in endothelial cell layers and in tissues undergoing active remodeling. It is heterotrimer comprised of alpha1(VIII) and alpha2(VIII) chains.
Binding Sites
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.
Biological Evolution
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.
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.
Osteogenesis Imperfecta
COLLAGEN DISEASES characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. Most types are autosomal dominant and are associated with mutations in COLLAGEN TYPE I.
Gene Expression Regulation, Developmental
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
Proline
Aminopropionitrile
Mutation
Sequence Alignment
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
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.
Collagen Type XIII
Integrin alpha1beta1
Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.
Chondrocytes
Polymorphic cells that form cartilage.