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.
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).
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.
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.
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.
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.
A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.
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.
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).
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.
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.
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.
A family of structurally related collagens that form the characteristic collagen fibril bundles seen in CONNECTIVE TISSUE.
An integrin alpha subunit that primarily combines with INTEGRIN BETA1 to form the INTEGRIN ALPHA2BETA1 heterodimer. It contains a domain which has homology to collagen-binding domains found in von Willebrand factor.
A protease nexin and serpin subtype that is specific for several SERINE PROTEASES including UROKINASE; THROMBIN; TRYPSIN; and PLASMINOGEN ACTIVATORS.
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.
A fibrillar collagen found primarily in interstitial CARTILAGE. Collagen type XI is heterotrimer containing alpha1(XI), alpha2(XI) and alpha3(XI) subunits.
Adherence of cells to surfaces or to other cells.
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.
Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.
Acquired degenerative dilation or expansion (ectasia) of normal BLOOD VESSELS, often associated with aging. They are isolated, tortuous, thin-walled vessels and sources of bleeding. They occur most often in mucosal capillaries of the GASTROINTESTINAL TRACT leading to GASTROINTESTINAL HEMORRHAGE and ANEMIA.
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 cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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)
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains.
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.
A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
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.
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.
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
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.
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.
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.
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.
A non-fibrillar collagen found primarily in terminally differentiated hypertrophic CHONDROCYTES. It is a homotrimer of three identical alpha1(X) subunits.
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.
A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.
A fibril-associated collagen found in many tissues bearing high tensile stress, such as TENDONS and LIGAMENTS. It is comprised of a trimer of three identical alpha1(XII) chains.
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.
Enzymes that catalyze the degradation of collagen by acting on the peptide bonds.
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)
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
The thin membranous structure supporting the adjoining glomerular capillaries. It is composed of GLOMERULAR MESANGIAL CELLS and their EXTRACELLULAR MATRIX.
An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
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)
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.
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.
Physicochemical property of fimbriated (FIMBRIAE, BACTERIAL) and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Glycoproteins which have a very high polysaccharide content.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The deformation and flow behavior of BLOOD and its elements i.e., PLASMA; ERYTHROCYTES; WHITE BLOOD CELLS; and BLOOD PLATELETS.
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.
A fibril-associated collagen usually found crosslinked to the surface of COLLAGEN TYPE II fibrils. It is a heterotrimer containing alpha1(IX), alpha2(IX) and alpha3(IX) subunits.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
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.
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.
Polymorphic cells that form cartilage.
PROGESTERONE-producing cells in the CORPUS LUTEUM. The large luteal cells derive from the GRANULOSA CELLS. The small luteal cells derive from the THECA CELLS.
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.
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.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Elements of limited time intervals, contributing to particular results or situations.
Thin, hairlike appendages, 1 to 20 microns in length and often occurring in large numbers, present on the cells of gram-negative bacteria, particularly Enterobacteriaceae and Neisseria. Unlike flagella, they do not possess motility, but being protein (pilin) in nature, they possess antigenic and hemagglutinating properties. They are of medical importance because some fimbriae mediate the attachment of bacteria to cells via adhesins (ADHESINS, BACTERIAL). Bacterial fimbriae refer to common pili, to be distinguished from the preferred use of "pili", which is confined to sex pili (PILI, SEX).
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.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
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.
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.
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.
Basic glycoprotein members of the SERPIN SUPERFAMILY that function as COLLAGEN-specific MOLECULAR CHAPERONES in the ENDOPLASMIC RETICULUM.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
A group of inherited conditions characterized initially by HEMATURIA and slowly progressing to RENAL INSUFFICIENCY. The most common form is the Alport syndrome (hereditary nephritis with HEARING LOSS) which is caused by mutations in genes for TYPE IV COLLAGEN and defective GLOMERULAR BASEMENT MEMBRANE.
A hydroxylated derivative of the amino acid LYSINE that is present in certain collagens.
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.
Glycoproteins found on the membrane or surface of cells.
A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-.
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.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Proteins that are structural components of bacterial fimbriae (FIMBRIAE, BACTERIAL) or sex pili (PILI, SEX).
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.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
A layer of the cornea. It is the basal lamina of the CORNEAL ENDOTHELIUM (from which it is secreted) separating it from the CORNEAL STROMA. It is a homogeneous structure composed of fine collagenous filaments, and slowly increases in thickness with age.
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.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. The use of TISSUE SCAFFOLDING enables the generation of complex multi-layered tissues and tissue structures.
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.
A hypertriglyceridemia disorder, often with autosomal dominant inheritance. It is characterized by the persistent elevations of plasma TRIGLYCERIDES, endogenously synthesized and contained predominantly in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins). In contrast, the plasma CHOLESTEROL and PHOSPHOLIPIDS usually remain within normal limits.
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)
Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or N-acetylgalactosamine.
An autosomal recessive metabolic disorder due to a deficiency in expression of glycogen branching enzyme 1 (alpha-1,4-glucan-6-alpha-glucosyltransferase), resulting in an accumulation of abnormal GLYCOGEN with long outer branches. Clinical features are MUSCLE HYPOTONIA and CIRRHOSIS. Death from liver disease usually occurs before age 2.
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.
A mixed-function oxygenase that catalyzes the hydroxylation of peptidyllysine, usually in protocollagen, to peptidylhydroxylysine. The enzyme utilizes molecular oxygen with concomitant oxidative decarboxylation of the cosubstrate 2-oxoglutarate to succinate. EC
The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.
The formation of cartilage. This process is directed by CHONDROCYTES which continually divide and lay down matrix during development. It is sometimes a precursor to OSTEOGENESIS.
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.
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.
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.
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.
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.
The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.
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.
Restoration of integrity to traumatized tissue.
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.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes.
Proteins found in any species of bacterium.
The lamellated connective tissue constituting the thickest layer of the cornea between the Bowman and Descemet membranes.
A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.
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.
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.
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.
A family of structurally-related short-chain collagens that do not form large fibril bundles.
A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.
A small leucine-rich proteoglycan found in a variety of tissues including CAPILLARY ENDOTHELIUM; SKELETAL MUSCLE; CARTILAGE; BONE; and TENDONS. The protein contains two glycosaminoglycan chains and is similar in structure to DECORIN.
Filamentous or elongated proteinaceous structures which extend from the cell surface in gram-negative bacteria that contain certain types of conjugative plasmid. These pili are the organs associated with genetic transfer and have essential roles in conjugation. Normally, only one or a few pili occur on a given donor cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed, p675) This preferred use of "pili" refers to the sexual appendage, to be distinguished from bacterial fimbriae (FIMBRIAE, BACTERIAL), also known as common pili, which are usually concerned with adhesion.
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.
ARTHRITIS that is induced in experimental animals. Immunological methods and infectious agents can be used to develop experimental arthritis models. These methods include injections of stimulators of the immune response, such as an adjuvant (ADJUVANTS, IMMUNOLOGIC) or COLLAGEN.
An integrin alpha subunit that binds COLLAGEN and LAMININ though its I domain. It combines with INTEGRIN BETA1 to form the heterodimer INTEGRIN ALPHA1BETA1.
A non-fibrillar collagen found as a ubiquitously expressed membrane- associated protein. Type XIII collagen contains both collagenous and non-collagenous domains along with a transmembrane domain within its N-terminal region.
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.
A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.
Proteins prepared by recombinant DNA technology.
Methods for maintaining or growing CELLS in vitro.
Chemicals with two conjoined aromatic rings incorporating two nitrogen atoms and one of the carbons oxidized with a keto oxygen.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Proteoglycans consisting of proteins linked to one or more CHONDROITIN SULFATE-containing oligosaccharide chains.
A mixed-function oxygenase that catalyzes the hydroxylation of a prolyl-glycyl containing peptide, usually in PROTOCOLLAGEN, to a hydroxyprolylglycyl-containing-peptide. The enzyme utilizes molecular OXYGEN with a concomitant oxidative decarboxylation of 2-oxoglutarate to SUCCINATE. The enzyme occurs as a tetramer of two alpha and two beta subunits. The beta subunit of procollagen-proline dioxygenase is identical to the enzyme PROTEIN DISULFIDE-ISOMERASES.
The process of bone formation. Histogenesis of bone including ossification.
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.
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.
Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
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.
An autoimmune disease of the KIDNEY and the LUNG. It is characterized by the presence of circulating autoantibodies targeting the epitopes in the non-collagenous domains of COLLAGEN TYPE IV in the basement membranes of kidney glomeruli (KIDNEY GLOMERULUS) and lung alveoli (PULMONARY ALVEOLI), and the subsequent destruction of these basement membranes. Clinical features include pulmonary alveolar hemorrhage and glomerulonephritis.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
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.
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.
The rate dynamics in chemical or physical systems.
The sum of the weight of all the atoms in a molecule.
The maximum stress a material subjected to a stretching load can withstand without tearing. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed, p2001)
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
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.
Connective tissue comprised chiefly of elastic fibers. Elastic fibers have two components: ELASTIN and MICROFIBRILS.
Antibodies produced by a single clone of cells.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
The white, opaque, fibrous, outer tunic of the eyeball, covering it entirely excepting the segment covered anteriorly by the cornea. It is essentially avascular but contains apertures for vessels, lymphatics, and nerves. It receives the tendons of insertion of the extraocular muscles and at the corneoscleral junction contains the canal of Schlemm. (From Cline et al., Dictionary of Visual Science, 4th ed)
Any of the 23 plates of fibrocartilage found between the bodies of adjacent VERTEBRAE.
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.
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.
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).
An enzyme oxidizing peptidyl-lysyl-peptide in the presence of water & molecular oxygen to yield peptidyl-allysyl-peptide plus ammonia & hydrogen peroxide. EC
One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.
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).
Perisinusoidal cells of the liver, located in the space of Disse between HEPATOCYTES and sinusoidal endothelial cells.
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.
In GRAM NEGATIVE BACTERIA, multiprotein complexes that function to translocate pathogen protein effector molecules across the bacterial cell envelope, often directly into the host. These effectors are involved in producing surface structures for adhesion, bacterial motility, manipulation of host functions, modulation of host defense responses, and other functions involved in facilitating survival of the pathogen. Several of the systems have homologous components functioning similarly in GRAM POSITIVE BACTERIA.
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC
Synthetic or natural materials, other than DRUGS, that are used to replace or repair any body TISSUES or bodily function.
The area between the EPIPHYSIS and the DIAPHYSIS within which bone growth occurs.
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.
A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (CICATRIX, HYPERTROPHIC) in that the former does not spread to surrounding tissues.
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)
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.
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
A group of cells that includes FIBROBLASTS, cartilage cells, ADIPOCYTES, smooth muscle cells, and bone cells.
Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.
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.
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.
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.
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.
A species of gram-negative, aerobic bacteria isolated from soil and the stems, leafs, and roots of plants. Some biotypes are pathogenic and cause the formation of PLANT TUMORS in a wide variety of higher plants. The species is a major research tool in biotechnology.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
Reagent used as an intermediate in the manufacture of beta-alanine and pantothenic acid.
Peptides composed of between two and twelve amino acids.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
A scleroprotein fibril consisting mostly of type III collagen. Reticulin fibrils are extremely thin, with a diameter of between 0.5 and 2 um. They are involved in maintaining the structural integrity in a variety of organs.
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)
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.
A group of inherited metabolic diseases characterized by the accumulation of excessive amounts of acid mucopolysaccharides, sphingolipids, and/or glycolipids in visceral and mesenchymal cells. Abnormal amounts of sphingolipids or glycolipids are present in neural tissue. INTELLECTUAL DISABILITY and skeletal changes, most notably dysostosis multiplex, occur frequently. (From Joynt, Clinical Neurology, 1992, Ch56, pp36-7)

Goodpasture antigen: expression of the full-length alpha3(IV) chain of collagen IV and localization of epitopes exclusively to the noncollagenous domain. (1/975)

BACKGROUND: Tissue injury in Goodpasture (GP) syndrome (rapidly progressive glomerular nephritis and pulmonary hemorrhage) is mediated by antibasement membrane antibodies that are targeted to the alpha3(IV) chain of type IV collagen, one of five alpha(IV) chains that occur in the glomerular basement membrane. GP antibodies are known to bind epitopes within the carboxyl terminal noncollagenous domain (NC1) of the alpha3(IV) chain, termed the GP autoantigen. Whether epitopes also exist in the 1400-residue collagenous domain is unknown because studies to date have focused solely on the NC1 domain. A knowledge of GP epitopes is important for the understanding of the etiology and pathogenesis of the disease and for the development of therapeutic strategies. METHODS: A cDNA construct was prepared for the full-length human alpha3(IV) chain. The construct was stably transfected into human embryonic kidney 293 cells. The purified full-length r-alpha3(IV) chain was characterized by electrophoresis and electron microscopy. The capacity of this chain for binding of GP antibodies from five patients was compared with that of the human r-alpha3(IV)NC1 domain by competitive enzyme-linked immunosorbent assay. RESULTS: The r-alpha3(IV) chain was secreted from 293 cells as a single polypeptide chain that did not spontaneously undergo assembly into a triple-helical molecule. An analysis of GP-antibody binding to the full-length r-alpha3(IV) chain showed binding exclusively to the globular NC1 domain. CONCLUSION: The full-length human alpha3(IV) chain possesses the capacity to bind GP autoantibodies. The epitope(s) is found exclusively on the nontriple-helical NC1 domain of the alpha3(IV) chain, indicating the presence of specific immunogenic properties. The alpha3(IV) chain alone does not spontaneously undergo assembly into a triple-helical homotrimeric molecule, suggesting that coassembly with either the alpha4(IV) and/or the alpha5(IV) chain may be required for triple-helix formation.  (+info)

Identification of a clinically relevant immunodominant region of collagen IV in Goodpasture disease. (2/975)

BACKGROUND: The characteristic feature of Goodpasture disease is the occurrence of an autoantibody response to the noncollagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] in the alveolar and glomerular basement membrane. These antibodies are associated with the development of a rapidly progressive glomerulonephritis, with or without lung hemorrhage, whereas autoantibodies specific for the other alpha chains of the heterotrimeric type IV collagen probably do not cause disease. In this study, we have investigated whether differences in fine specificity of autoimmune recognition of the alpha3(IV)NC1 correlate with clinical outcome. METHODS: For mapping of antibody binding to type IV collagen, chimeric collagen constructs were generated in which parts of the alpha3(IV)NC1 domain were replaced by the corresponding sequences of homologous nonreactive alpha1(IV). The different recombinant collagen chimeras allowed the analysis of antibody specificities in 77 sera from well-documented patients. RESULTS: One construct that harbors the aminoterminal third of the alpha3(IV)NC1 was recognized by all sera, indicating that it represents the dominant target of the B-cell response in Goodpasture disease. Seventy percent of the samples recognized other parts of the molecule as well. However, only reactivity to the N-terminus of the alpha3(IV)NC1 correlated with prognosis, that is, kidney survival after six months of follow-up. CONCLUSION: The results indicate the crucial importance of antibody recognition of this particular domain for the pathogenesis of Goodpasture disease, thereby opening new avenues for the development of better diagnostic and therapeutic procedures.  (+info)

The goodpasture autoantigen. Mapping the major conformational epitope(s) of alpha3(IV) collagen to residues 17-31 and 127-141 of the NC1 domain. (3/975)

The Goodpasture (GP) autoantigen has been identified as the alpha3(IV) collagen chain, one of six homologous chains designated alpha1-alpha6 that comprise type IV collagen (Hudson, B. G., Reeders, S. T., and Tryggvason, K. (1993) J. Biol. Chem. 268, 26033-26036). In this study, chimeric proteins were used to map the location of the major conformational, disulfide bond-dependent GP autoepitope(s) that has been previously localized to the noncollagenous (NC1) domain of alpha3(IV) chain. Fourteen alpha1/alpha3 NC1 chimeras were constructed by substituting one or more short sequences of alpha3(IV)NC1 at the corresponding positions in the non-immunoreactive alpha1(IV)NC1 domain and expressed in mammalian cells for proper folding. The interaction between the chimeras and eight GP sera was assessed by both direct and inhibition enzyme-linked immunosorbent assay. Two chimeras, C2 containing residues 17-31 of alpha3(IV)NC1 and C6 containing residues 127-141 of alpha3(IV)NC1, bound autoantibodies, as did combination chimeras containing these regions. The epitope(s) that encompasses these sequences is immunodominant, showing strong reactivity with all GP sera and accounting for 50-90% of the autoantibody reactivity toward alpha3(IV)NC1. The conformational nature of the epitope(s) in the C2 and C6 chimeras was established by reduction of the disulfide bonds and by PEPSCAN analysis of overlapping 12-mer peptides derived from alpha1- and alpha3(IV)NC1 sequences. The amino acid sequences 17-31 and 127-141 in alpha3(IV)NC1 have thus been shown to contain the critical residues of one or two disulfide bond-dependent conformational autoepitopes that bind GP autoantibodies.  (+info)

Characterization of a novel type of serine/threonine kinase that specifically phosphorylates the human goodpasture antigen. (4/975)

Goodpasture disease is an autoimmune disorder that occurs naturally only in humans. Also exclusive to humans is the phosphorylation process that targets the unique N-terminal region of the Goodpasture antigen. Here we report the molecular cloning of GPBP (Goodpasture antigen-binding protein), a previously unknown 624-residue polypeptide. Although the predicted sequence does not meet the conventional structural requirements for a protein kinase, its recombinant counterpart specifically binds to and phosphorylates the exclusive N-terminal region of the human Goodpasture antigen in vitro. This novel kinase is widely expressed in human tissues but shows preferential expression in the histological structures that are targets of common autoimmune responses. The work presented in this report highlights a novel gene to be explored in human autoimmunity.  (+info)

The goodpasture autoantigen. Identification of multiple cryptic epitopes on the NC1 domain of the alpha3(IV) collagen chain. (5/975)

Goodpasture (GP) disease is an autoimmune disorder in which autoantibodies against the alpha3(IV) chain of type IV collagen bind to the glomerular and alveolar basement membranes, causing progressive glomerulonephritis and pulmonary hemorrhage. Two major conformational epitope regions have been identified on the noncollagenous domain of type IV collagen (NC1 domain) of the alpha3(IV) chain as residues 17-31 (E(A)) and 127-141 (E(B)) (Netzer, K.-O. et al. (1999) J. Biol. Chem. 274, 11267-11274). To determine whether these regions are two distinct epitopes or form a single epitope, three GP sera were fractionated by affinity chromatography on immobilized NC1 chimeras containing the E(A) and/or the E(B) region. Four subpopulations of GP antibodies with distinct epitope specificity for the alpha3(IV)NC1 domain were thus separated and characterized. They were designated GP(A), GP(B), GP(AB), and GP(X), to reflect their reactivity with E(A) only, E(B) only, both regions, and neither, respectively. Hence, regions E(A) and E(B) encompass critical amino acids that constitute three distinct epitopes for GP(A), GP(B), and GP(AB) antibodies, respectively, whereas the epitope for GP(X) antibodies is located in a different unknown region. The GP(A) antibodies were consistently immunodominant, accounting for 60-65% of the total immunoreactivity to alpha3(IV)NC1; thus, they probably play a major role in pathogenesis. Regions E(A) and E(B) are held in close proximity because they jointly form the epitope for Mab3, a monoclonal antibody that competes for binding with GP autoantibodies. All GP epitopes are sequestered in the hexamer configuration of the NC1 domain found in tissues and are inaccessible for antibody binding unless dissociation of the hexamer occurs, suggesting a possible mechanism for etiology of GP disease. GP antibodies have the capacity to extract alpha3(IV)NC1 monomers, but not dimers, from native human glomerular basement membrane hexamers, a property that may be of fundamental importance for the pathogenesis of the disease.  (+info)

Distinct antitumor properties of a type IV collagen domain derived from basement membrane. (6/975)

Vascular basement membrane is an important structural component of blood vessels. During angiogenesis this membrane undergoes many alterations and these changes are speculated to influence the formation of new capillaries. Type IV collagen is a major component of vascular basement membrane, and recently we identified a fragment of type IV collagen alpha2 chain with specific anti-angiogenic properties (Kamphaus, G. D., Colorado, P. C., Panka, D. J., Hopfer, H., Ramchandran, R., Torre, A., Maeshima, Y., Mier, J. W., Sukhatme, V. P., and Kalluri, R. (2000) J. Biol. Chem. 275, 1209-1215). In the present study we characterize two different antitumor activities associated with the noncollagenous 1 (NC1) domain of the alpha3 chain of type IV collagen. This domain was previously discovered to possess a C-terminal peptide sequence (amino acids 185-203) that inhibits melanoma cell proliferation (Han, J., Ohno, N., Pasco, S., Monboisse, J. C., Borel, J. P., and Kefalides, N. A. (1997) J. Biol. Chem. 272, 20395-20401). In the present study, we identify the anti-angiogenic capacity of this domain using several in vitro and in vivo assays. The alpha3(IV)NC1 inhibited in vivo neovascularization in matrigel plug assays and suppressed tumor growth of human renal cell carcinoma (786-O) and prostate carcinoma (PC-3) in mouse xenograft models associated with in vivo endothelial cell-specific apoptosis. The anti-angiogenic activity was localized to amino acids 54-132 using deletion mutagenesis. This anti-angiogenic region is separate from the 185-203 amino acid region responsible for the antitumor cell activity. Additionally, our experiments indicate that the antitumor cell activity is not realized until the peptide region is exposed by truncation of the alpha3(IV)NC1 domain, a requirement not essential for the anti-angiogenic activity of this domain. Collectively, these results effectively highlight the distinct and unique antitumor properties of the alpha3(IV)NC1 domain and the potential use of this molecule for inhibition of tumor growth.  (+info)

Two RGD-independent alpha vbeta 3 integrin binding sites on tumstatin regulate distinct anti-tumor properties. (7/975)

Vascular basement membrane is an important regulator of angiogenesis and undergoes many alterations during angiogenesis and these changes are speculated to influence neovascularization. Recently, fragments of collagen molecules have been identified to possess anti-angiogenic activity. Tumstatin (alpha3(IV)NC1 domain) is one such novel molecule with distinct anti-tumor properties and possesses an N-terminal (amino acids 54-132) anti-angiogenic and a C-terminal (amino acids 185-203) anti-tumor cell activity (Maeshima, Y., et al. 2000) J. Biol. Chem. 275, 21340-21348). Previous studies have identified the 185-203 amino acid sequence as a ligand for alpha(v)beta(3) integrin (Shahan, T. A., et al. (1999) Cancer Res. 59, 4584-4590). In the present study, we found distinct additional RGD-independent alpha(v)beta(3) integrin binding site within 54-132 amino acids of tumstatin. This site is not essential for inhibition of tumor cell proliferation but necessary for the anti-angiogenic activity. A fragment of tumstatin containing 54-132 amino acid (tum-2) binds both endothelial cells and melanoma cells but only inhibited proliferation of endothelial cells, with no effect on tumor cell proliferation. A similar experiment with fragment of tumstatin containing the 185-203 amino acid (tum-4) demonstrates that it binds both endothelial cells and melanoma cells but only inhibits the proliferation of melanoma cells. The presence of cyclic RGD peptides did not affect the alpha(v)beta(3) integrin-mediated activity of tumstatin, although significant inhibition of endothelial cell binding to vitronectin was observed. The two distinct RGD-independent binding sites on tumstatin suggest unique alpha(v)beta(3) integrin-mediated mechanisms governing the two distinct anti-tumor properties of tumstatin.  (+info)

High affinity of anti-GBM antibodies from Goodpasture and transplanted Alport patients to alpha3(IV)NC1 collagen. (8/975)

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) antibody-mediated diseases are characterized by rapidly progressive glomerulonephritis (RPGN) that often results in irreversible loss of renal function and renal failure. Although many factors contribute to the fulminant nature and treatment resistance of this disease, we questioned whether high affinity autoantibody-alpha3(IV) collagen interactions lead to persistent antibody deposition, thereby perpetuating inflammation. To address this hypothesis, the binding kinetics of human anti-GBM antibodies (Ab) to alpha3(IV)NC1 were evaluated using an optical biosensor interaction analysis. METHODS: Polyclonal anti-GBM Abs were purified by alpha3(IV)NC1 affinity chromatography from the sera of patients with anti-GBM AB-mediated diseases, including individuals with Goodpasture syndrome (GS), idiopathic RPGN (N = 7), and Alport syndrome (AL) following kidney transplantation (N = 4). The affinity-binding characteristics of the autoantibodies were determined using a biosensor analysis system, with immobilized bovine alpha3(IV)NC1 dimers. RESULTS: All of the autoantibody preparations bound to alpha3(IV)NC1, whereas none bound to alpha1(IV)NC1 (control). Purified, normal serum IgG did not bind to either antigen. Estimated dissociation constants (Kd) for the purified autoantibodies were 1.39E-04 +/- 7.30E-05 s-l (GS) and 8. 90E-05 +/- 2.80E-05 s-l (AL). Their estimated association constants (Ka) were 2.67E+04 +/- 1.8E+04 (M-ls-l) and 2.76E+04 +/- 1. 70E+04(M-ls-l) for GS and AL patients, respectively. By comparison with other Ab interactions, these Abs demonstrated high affinity, with relatively high on (binding) rates and slow off (dissociation) rates. CONCLUSIONS: The results suggest that anti-GBM Abs bind rapidly and remain tightly bound to the GBM in vivo. This property likely contributes to both the fulminant nature of this disease and its resistance to therapy, because persistent glomerular Ab deposition has the potential to produce continuous inflammation, despite removal of circulating Abs and adequate immunosuppression.  (+info)

Results In Caco-2 cells an ∼ 18-fold increase (p,0.0001) in DP IV protein expression was seen after incubation with TNFα at a concentration of 25 ng/μl for 48 h, as compared to untreated cells. This change is mirrored at the mRNA level with a twofold increase in DP IV expression at similar TNFα concentration and time course. Similar changes were noted in human tissue with a significant 4.5-fold DP IV upregulation (p=0.02) in CD compared to normal controls. However, results at the protein level in human tissue showed an opposite trend, with a ∼2.7-fold decrease in DP IV expression in CD tissue compared to controls (p=0.05). The highest DP IV fasting plasma levels were noted in the control group (558.5±39.98 ng/ml). Levels in CD were significantly less (p=0.0028) both in large bowel CD (406.2±48.10 ng/ml) and more so in the small bowel CD group (361.3±38.83 ng/ml; p,0.01). There was no significant difference in plasma DP IV between active and inactive disease.. ...
I have two renal pathologists interested in collagen IV alpha 3 and alpha 5 Alports syndrome. I would like a vendor/distributor in the US if possible and any protocols would be helpful. Thanks and I hope everyone is having a great week ...
A genome-wide association study (GWAS) was conducted to identify expression quantitative trait loci (eQTLs) for the genes involved in phosphatidylinositol-3-kinase/v-akt murine thymoma viral oncogene homolog (PI3K/AKT) pathway.Data on mRNA expression of 341 genes in lymphoblastoid cell lines of 373 Europeans recruited by the 1000 Genomes Project using Illumina HiSeq2000 were utilized. We used their genotypes at 5,941,815 nucleotide variants obtained by Genome Analyzer II and SOLiD.The association analysis revealed 4166 nucleotide variants associated with expression of 85 genes (P < 5 × 10). A total of 73 eQTLs were identified as association signals for the expression of multiple genes. They included 9 eQTLs for both of the genes encoding collagen type I alpha 1 (COL1A1) and integrin alpha 11 (ITGA11), which synthesize a major complex of plasma membrane. They also included eQTLs for type IV collagen molecules; 13 eQTLs for both collagen type IV alpha 1 (COL4A1) and collagen type IV alpha 2 ...
Type-IV collagen is a type of collagen found primarily in the basal lamina. The C-terminus domain is not removed in post-translational processing, and the fibers link head-to-head, rather than in parallel. Also, type-IV lacks the regular glycine in every third residue necessary for the tight, collagen helix. This makes the overall arrangement more sloppy with kinks. These two features cause the collagen to form in a sheet, the form of the basal lamina The alpha 3 protein constituent of type-IV collagen is thought to be the antigen implicated in goodpastures syndrome, wherein the immune system attacks the basement membranes of the glomeruli and the alveoli. There are six human genes associated with it: ...
Fingerprint Dive into the research topics of Alveolar basement membrane: molecular properties of the noncollagenous domain (hexamer) of collagen IV and its reactivity with Goodpasture autoantibodies.. Together they form a unique fingerprint. ...
Mouse monoclonal antibody raised against full length native collagen type IV. Native purified human collagen type IV. (MAB1562) - Products - Abnova
TGF-β/Smad signaling plays an important role in diabetic nephropathy. The present study identified a novel Smad3-dependent long non-coding RNA (lncRNA) Erbb4-IR in the development of type-2 diabetic nephropathy (T2DN) in db/db mice. We found that Erbb4-IR was highly expressed in T2DN of db/db mice and was specifically induced by AGE via a Smad3-dependent mechanism. The functional role of Erbb4-IR in T2DN was revealed by kidney-specific silencing of Erbb4-IR to protect against the development of T2DN such as elevated microalbuminuria, serum creatinine and progressive renal fibrosis in db/db mice, and to block AGE-induced collagen I and IV expression in mouse mesangial cells (mMCs) and mouse tubular epithelial cells (mTECs). Mechanistically, we identified that the Erbb4-IR-miR-29b axis was a key mechanism of T2DN because Erbb4-IR was able to bind the 3UTR of miR-29b genomic sequence to suppress miR-29b expression at transcriptional level. In contrast, silencing of renal Erbb4-IR increased ...
We have shown that the adhesion of human fetal β-cells to a variety of matrix constituents results in enhanced insulin secretion. Two of these constituents, vitronectin and collagen IV, induced the highest levels of secretion, and this secretion was shown to be both ERK and integrin dependent. The matrix-induced insulin secretion observed was glucose independent and appeared to be unregulated because it ultimately resulted in a significant depletion of insulin content. Additional studies using adult islets showed that mature β-cells also lose insulin content on collagen IV, but they are unaffected by vitronectin. Using real-time PCR, we have shown that adhesion of fetal and adult β-cells to select substrates (vitronectin, collagen IV, and HTB-9 matrix) also significantly suppresses insulin gene transcription. The loss of insulin production and content described in this study was not found to be associated with cell death.. Based on our findings, a variety of integrin-matrix interactions would ...
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IV. 喉動態鏡檢查4主要用於了解聲帶振動狀況》由於喉動態鏡具有與聲帶振動頻率一致並同步的光源3檢查時可以觀察聲帶的振動方式3幅度等》正常情況下3發低音時3聲帶振動速度慢3振幅大4發高音時3聲帶振動速度快3振幅小4兩側聲帶呈對稱性3波浪形運動3聲帶振動速度均勻》聲帶有病變時3根據病情輕重3表現為振動速度變慢3振幅減少3聲帶波浪形運動減弱或消失3兩側常不對稱》 ...
Goodpastures disease is a rare immunological disease with formation of pathognomonic antibodies against renal and pulmonary basement membranes. Cerebral involvement has been reported in several cases in the literature, yet the pathogenetic mechanism is not entirely clear. A 21-year-old Caucasian man with Goodpastures disease and end-stage renal disease presented with two generalized seizures after a period of mild cognitive disturbance. Blood pressure and routine laboratory tests did not exceed the patients usual values, and examination of cerebrospinal fluid was unremarkable. Cerebral magnetic resonance imaging (MRI) revealed multiple cortical and subcortical lesions on fluid-attenuated inversion recovery sequences. Since antiglomerular basement membrane antibodies were found to be positive with high titers, plasmapheresis was started. In addition, cyclophosphamide pulse therapy was given on day 13. Encephalopathy and MRI lesions disappeared during this therapy, and antiglomerular basement membrane
Normal glomerular capillaries filter plasma through a basement membrane (GBM) rich in alpha3(IV), alpha4(IV), and alpha5(IV) chains of type IV collagen. We now show that these latter isoforms are absent biochemically from the glomeruli in patients with X-linked Alport syndrome (XAS). Their GBM inste …
Principal Investigator:YOSHIOKA Kazuo, Project Period (FY):1995 - 1996, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Pediatrics
Alport syndrome is a genetic disorder affecting around 1 in 50,000 children, characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. Alport syndrome can also affect the eyes, though the changes do not usually affect sight, except when changes to the lens occur in later life. Blood in urine is universal. Proteinuria is a feature as kidney disease progresses. The disorder was first identified in a British family by University of Edinburgh Medical School graduate Cecil A. Alport in 1927. Alport Syndrome once also had the label hereditary nephritis, but this is misleading as there are many other causes of hereditary kidney disease and nephritis. Alport syndrome is caused by an inherited defect in type IV collagen-a structural material that is needed for the normal function of different parts of the body. Since type IV collagen is found in the ears, eyes, and kidneys, this explains why Alport syndrome affects different seemingly unrelated parts of the body (ears, eyes, ...
Sigma-Aldrich offers EMD Millipore-ECM105, Millicoat™ Human Collagen Type IV Coated Strips (96-Wells) for your research needs. Find product specific information including CAS, MSDS, protocols and references.
Alport syndrome is a hereditary disease characterized by hematuria. Alport syndrome is mostly an X-linked disorder but autosomal recessive Alport syndrome has been described.
Goodpasture syndrome is a rare autoimmune disease that affects the lungs and kidneys. Normally, the immune system makes antibodies to fight off germs. With Goodpasture syndrome, however, the immune system mistakenly makes antibodies that attack the lungs and kidneys. This condition can quickly progress to glomerulonephritis and kidney failure.
Goodpasture syndrome is a rare autoimmune disease that affects the lungs and kidneys. Normally, the immune system makes antibodies to fight off germs. With Goodpasture syndrome, however, the immune system mistakenly makes antibodies that attack the lungs and kidneys. This condition can quickly progress to glomerulonephritis and kidney failure.
Goodpasture syndrome is a rare autoimmune disease that affects the lungs and kidneys. Normally, the immune system makes antibodies to fight off germs. With Goodpasture syndrome, however, the immune system mistakenly makes antibodies that attack the lungs and kidneys. This condition can quickly progress to glomerulonephritis and kidney failure.
Alports syndrome (awl-ports) n. a hereditary disease that causes nephritis accompanied by deafness. Affected males usually develop end-stage renal failure and, unless treated with a kidney transplant, die before the age of 40. Females have a better prognosis.[ A. C. Alport (1880-1959), South African physician] Source for information on Alports syndrome: A Dictionary of Nursing dictionary.
Mutations in the genes COL4A3, COL4A4, and COL4A5 affect the synthesis, assembly, deposition, or function of the collagen IV α345 molecule, the major collagenous constituent of the mature mammalian glomerular basement membrane. These mutations are associated with a spectrum of nephropathy, from micr …
View the Goodpasture surname, family crest and coat of arms. Discover the Goodpasture family history for the Dutch Origin. What is the origin of the name Goodpasture?
Traveling can be a challenge for Alport syndrome patients. There are several things patients and their families should consider before taking a trip.
Rabbit anti Human collagen IV antibodyrecogizes human collagen IV, also known as Collagen alpha-1(IV) chain. Collagen IV is a 1497 amino a
Alport syndrome (AS) represents a form of progressive hereditary nephritis in which the genetic defect resides in the synthesis of one of several subunits of type IV collagen, the predominant constituent of basement membranes in renal glomeruli. Renal impairment occurs with time and severe renal failure with hypertension and uremia represent the end stage of the disease, even if a high variability in the rate of progression is described.Males are usually affected by a progressive form of the disease. Affected females with X-linked syndrome usually have a good prognosis with a mild renal impairment. The disease is also associated to a sensor neural deafness which can occur in approximately half of the patient affected and usually correlates with renal impairment. No definite treatment exists in order to delay the time of dialysis or a kidney transplant. Many studies showed that Angiotensin converting enzyme (ACE) inhibitors slow glomerular filtration rate (GFR) decline and limit progression to ...
Gentaur molecular products has all kinds of products like :search , AbD \ RABBIT ANTI HUMAN COLLAGEN IV, Product Type Polyclonal Antibody, Specificity COLLAGEN IV, Target Species Human, Host Rabbit, Format Purified, Isotypes Polyclonal IgG, Applications C, E, IF, P*, \ 2150-0140 for more molecular products just contact us
Proteolysis is essential during branching morphogenesis but the functions of MT-MMPs and their proteolytic products are not clearly understood. into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV P505-15 is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis. 8 and 2-fold whereas and did not change (Physique […]. ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
If you are a subscriber to JASN you can obtain full text of this paper by clicking on the J Am Soc Nephrol hyperlink just above the title of the article ...
Read about the 15 new mutations and two new deletions that have been identified in three genes that encode for collagen in Alport syndrome patients.
In todays Art of Medicine post, Dr. Caza brings us electron microscopy images of a case of Alport syndrome. For more Art of Medicine posts, visit our blog!
Dr. Bellot responded: Immunosuppression. Since the condition is produced by an abnormal immune response, the treatment is to reduce production of the |a href=/topics/antibody track_data={
Micrographs of immunohistochemical staining of type IV collagen.Red arrowheads indicate the basement membrane of epidermis and green arrowheads indicate the bas
An inherited disorder involving damage to the kidney, blood in the urine, and in some families loss of hearing. The disorder may also include loss of vision.
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Reporting of immunofluorescent (IF) double staining for alpha 2 and alpha 5 chains of type IV collagen on kidney biopsies:. 1) Normal pattern of staining (ie, preserved linear alpha 5 staining of glomerular basement membranes, Bowman capsule, and distal tubular basement membranes). This pattern of staining is seen in normal individuals and patients with thin glomerular basement membrane disease but does not exclude the diagnosis of hereditary nephritis/Alport syndrome.. 2) Consistent with X-linked hereditary nephritis (Alport syndrome). There is global or segmental loss of alpha 5 staining of glomerular basement membranes, Bowman capsule, and distal tubular basement membranes. This pattern of loss of staining is usually due to mutations in the COL4A5 gene on the X chromosome.. 3) Consistent with autosomal hereditary nephritis (Alport syndrome). There is global or segmental loss of alpha 5 staining of glomerular basement membranes but preserved alpha 5 staining of Bowman capsule and distal ...
Alport syndrome is a genetically heterogeneous disorder with autosomal dominant, autosomal recessive and X-linked inheritance. The estimated prevalence is about 1 in 50,000 live births. All forms are caused by mutations in the genes encoding type IV collagen, which is a basement membrane component. Alport syndrome is characterized by a progressive glomerulonephropathy, sensorineural hearing loss and various ocular anomalies. The X-linked form represents about 85% of Alport syndrome cases and is caused by mutations in the COL4A5 gene. About 15% of cases are autosomal recessive, while autosomal dominant inheritance is rare. Diffuse leiomyomatosis with Alport syndrome represents a contiguous gene deletion syndrome involving the COL4A5 and COL4A6 genes.. Connective Tissue Gene Tests Alport syndrome NGS panel consists of four genes: COL4A3, COL4A4, COL4A5 and COL4A6.. Copy number variation (CNV) analysis of the Alport syndrome genes is also offered as a panel. Additionally, CTGT offers a ...
Goodpasture syndrome (GPS) is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure. It is thought to attack the alpha-3 subunit of type IV collagen, which has therefore been referred to as Goodpastures antigen. Goodpasture syndrome may quickly result in permanent lung and kidney damage, often leading to death. It is treated with immunosuppressant drugs such as corticosteroids and cyclophosphamide, and with plasmapheresis, in which the antibodies are removed from the blood. The disease was first described by an American pathologist Ernest Goodpasture of Vanderbilt University in 1919 and was later named in his honor. Play media The antiglomerular basement membrane (GBM) antibodies primarily attack the kidneys and lungs, although, generalized symptoms like malaise, weight loss, fatigue, fever, and chills are also common, as are joint aches and pains. 60 to 80% of those with the condition experience ...
This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset of basement membranes. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3 UTR ...
About 85% of Alport Syndrome (AS) cases have the classical X-linked pattern of inheritance similar to the family described by Dr. Alport. However, about 15% of cases follow a different genetic pattern. Basement membranes are actually a meshwork of many types of collagens and the genes for some of these other collagens are not located on the X-chromosome.. Patients with Autosomal Recessive Alport Syndrome (ARAS) have inherited a pair of abnormal collagen genes, one from each parent. In some families, the syndrome is caused by two mutant copies of a collagen gene termed Col 4A3; in other families, the Col 4A4 genes are defective. We now know that both of these collagen genes are located on chromosome #2, rather than on the X-chromosome. Consequently, both males and females are fully affected. Both these genes are important for integrity of the basement membrane; if either one is eliminated, there is progressive deterioration of renal function, deafness and changes in the eye, just as in ...
Alport syndrome is a genetic disorder affecting around 1 in 50,000 children, characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. Alport syndrome can also affect the eyes, though the changes do not usually affect sight, except when changes to the lens occur in later life. Blood in urine is universal. Proteinuria is a feature as kidney disease progresses.Wikipedia Alport syndrome is caused by mutations in the COL4A3, COL4A4, and COL4A5 genes, and over 1,500 mutations have been reported. In most people with Alport syndrome (about 85%), the condition is inherited in an X-linked pattern, due to mutations in the COL4A5 gene. Less commonly, the condition is inherited in an autosomal recessive pattern if both copies of the COL4A3 or COL4A4 gene, both located on chromosome 2, have been mutated.Wikipedia A form of Alport syndrome including the clinical symptoms of midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis was reported based on two (separate) ...
Goodpastures disease is a fulminant rapidly progressive disease characterized by autoantibodies to the alpha-3 chain of type IV collagen (Goodpastures antigen). It can ..
This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Collagen Type IV (COL4) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
We have recently shown that CA IV expression in kidney cortex increased five-fold at the mRNA level (35) and 3- to 5-fold at the protein level (25) during postnatal maturation. A previous study showed a 19-fold increase in CA IV mRNA expression in rat lung between fetal day 20 and postnatal day 6, and a 40% postnatal increase to day 17, with no further increase (7). The postnatal increase was nearly comparable to what we have observed in rabbit lung (Fig. 5B). However, the increase in CA IV mRNA in kidney cortex is at least 10-fold and likely to account for the postnatal increment in protein (24). With most of the increase occurring during postnatal weeks 3-5, it is likely that the increase reflects the change in eating habits and a shift to an alkaline ash diet that requires a renal adaptation in transport. The large increase in CA IV may allow the kidney to handle the maturational increase in filtered load of bicarbonate and its proximal reabsorption.. Detailed studies of CA IX expression ...
Purpose To study the effects of topical administration of 1% morphine on corneal analgesia in rabbits submitted to lamellar keratectomy and to assess the expression of matrix metalloproteinase-1, metalloproteinase-2, metalloproteinase-9 (MMPs), type IV collagen, and interleukin-10 (IL-10) during the treatment. Methods Morphine group (MG) received 50 mu L of topical 1% morphine four times daily, while the control group received saline instead. Corneal touch threshold (CTT) and the wound area were assessed until corneal healing. Corneal samples were processed for routine histology, immunohistochemistry, zymography, and ELISA. Results Following keratectomy, CTT increased significantly from 6 to 96 h time points. Mean corneal re-epithelization rate and scores of leukocyte infiltration did not differ significantly between treatment groups. Immunolabeling pattern for MMP-1, MMP-9, and type IV collagen was similar in both treatment groups. In the MG, zymography indicated significantly higher levels of ...
The Rep proteins encoded by the adeno-associated virus type 2 (AAV) play an essential role in the rescue, replication, and integration from the viral genome. 293 cells and analyzed for the to endure AAV DNA replication and rescue. Our studies uncovered that (i) a low-level recovery and autonomous replication from the wild-type AAV genome happened in 293 however, not in HeLa cells; (ii) mutations in the RBS led to augmented appearance through the p5 promoter, resulting in more efficient recovery and/or replication from the AAV genome in 293 however, not in HeLa cells; (iii) small recovery and/or replication happened from plasmids formulated with mutations in the YBS by itself in the lack of coinfection with adenovirus; (iv) expression of the adenovirus E1A gene products was insufficient to mediate rescue and/or replication of the AAV genome in HeLa cells; (v) autonomously replicated AAV genomes in 293 cells were successfully encapsidated in mature progeny virions that were biologically active in ...
Collagen IV is an abundant basement membrane protein which forms a polygonal net type structure with the lateral association of its C-terminal and N-terminal domains providing support and stability to the basement membrane against mechanical forces. Collagen IV is involved in human genetic diseases such as Good Pasture syndrome and Alports syndrome demonstrating the importance of functional collagen IV protein in the basement membrane. The current research attempted to identify a collagen IV cell surface receptor in C. elegans utilizing different Bioinformatics tools and methods like BLAST, PSI-BLAST, ELM, clustral multiple alignment, Motif scan, and wormbase. These protein databases and search strategies have identified candidate genes F35D2.3, C37C3.7, T25F10.3 encoded proteins with potential domains required to recognize collagen IV and to function as a cell surface receptor. RNA interference was used as a gene silence technique to test whether the putative proteins might function as cell surface
Goodpasture syndrome (also known as anti-GBM disease) is characterized by the presence of auto-antibodies to a component of lung and kidney tissue. It is an exceptionally rare disease, which impacts approximately 1 in every million people, though it is more common in white European and Asian populations. Goodpasture syndrome most typically presents as a combinations of lung and kidney problems although it can present less frequently as an isolated issue with either organ system. A patient such as ours, who presents with both coughing and urinating blood (known as hemoptysis and hematuria respectively) should at least prompt the consideration of Goodpasture syndrome in the differential diagnosis. Other symptoms of lung or kidney disease include chest pain with cough, high blood pressure, and swelling of the legs, all of which our patient had on initial presentation. Other nonspecific findings include fever, rash, fatigue, and an enlarged liver and spleen, all of which occur in much more common ...
Matrix metalloproteinases (MMPs) are a family of endopeptidases that collectively are capable to degrading all components of the extracellular matrix (ECM) and they have been implicated in several aspects of tumor progression, such as invasion through basement membrane (BM) and insterstitial matrices, angiogenesis and tumor cell growth. In particular, MMP-2 and MMP-9 have been associated with the ability of tumor cells to metastasize due to their capacity to degrade type IV collagen (Col-IV), the main component of BM, and to their elevated expression in malignant tumors. However, nothing is known about the regulation of MMP-9 secretion and expression in breast cancer cells stimulated with Col-IV. Our results demonstrate that stimulation of MCF-7 cells with Col-IV promoted the secretion of MMP-9, as revealed by gelatin zymography and Western blotting using specific antibodies that recognized MMP-9. In addition, inhibition of Src and FAK kinase activity prevented MMP-9 secretion. In contrast, MMP-9
In general, a neurologic assessment tool; findings are commonly faced with a space- prescription generic propecia no occupying lesion. Gitelman syndrome is inherited as an adjuvant setting has shown promising outcomes with noncompliance. 6. Provide adequate hydration if contrast will be possible. 4. Type i hypersensitivity causes local vasodilation and vasoconstriction), and nsaids unless they have a plan of excision of a rubbery consistency, it can easily be cured with treatments that leave no permanent disability. However, the age of the aortic bifurcation occlusion. 212 the surgical defect. Polychromatic platesdots of primary care provider for timely diagnosis and surgery. 7. Decrease in concentration, memory, and confu- sion. The cells , as this closure progresses. Maintaining fluid balance 1. Monitor temperature frequently or continuously according to facility protocol. Brown fat is bright. Although systemic thrombolysis for iliofemoral occlusion in an autosomal recessive alport syndrome ...
A GENESIS GUI for providing inputs to an auditory cortex model ======================================================================*/ //=============================== // Function Definitions //=============================== // Display the parameters for the specified input function show_params(input_num) str control_form = /input_control int input_num, row_num setfield {control_form}/input_num value {input_num} float frequency, delay, width, interval str pulse_src = {input_source} @ [ @ {input_num} @ ] @ /spikepulse str spike_out = {input_source} @ [ @ {input_num} @ ] @ /soma/spike // this assumes set_pulse_params has been called so that abs_refract != 0 row_num = {getfield {{input_source} @ [ @ {input_num} @ ]} input_row} setfield {control_form}/targ_row value {row_num} frequency = {getfield {{input_source} @ [ @ {input_num} @ ]} input_freq} setfield {control_form}/spikefreq value {frequency} delay = {getfield {pulse_src} delay1 } float width = {getfield {pulse_src} ...
As a wife of someone who will be having a kidney transplant soon, Im totally disgusted by this game show. What gives them the right to play God? What about the other 2 families that dont get the kidney? For them, it would be devistating....I guess they signed up for it and know that already. This should never be allowed to happen. Want to shine some light on the issue of organ shortage....go to Oprah or someone like that. My husband has a kidney disease called Alports Syndrome. He is 25 and his kidneys are not filtering toxins out of his blood as they should. It is X linked and passed genetically from his mom to him. In each of the one million tiny filtering units (glomeruli) in each kidney, blood is filtered across the glomerular basement membrane (GBM). In Alport syndrome, type IV collagen (collagen 4A5 gene in my husbands case), one of the proteins that makes up the GBM, is absent (my husbands) or abnormal. Although the GBM looks normal in childhood, it deteriorates with time because it ...
Alport syndrome is a rare condition that is caused by a mutation in one of the genes responsible for collagen production. Follow-up with a doctor can help reduce damage to various organs affected.
Alport syndrome is a rare condition that is caused by a mutation in one of the genes responsible for collagen production. Follow-up with a doctor can help reduce damage to various organs affected.
BD BioCoat Collagen IV 150 mm Culture Dishes from BD Biosciences - Discovery Labware,BD BioCoat Collagen IV 150 mm Culture Dishes,biological,biology supply,biology supplies,biology product
COL4A3 antibody (collagen, type IV, alpha 3 (Goodpasture antigen)) for ELISA, IHC-P, WB. Anti-COL4A3 pAb (GTX37323) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
Collagen IV Monoclonal Antibody from Invitrogen for Immunohistochemistry (Frozen), Immunohistochemistry (Paraffin) and ELISA applications. This antibody reacts with Human samples. Clone: MC4-HA. Supplied as 200 µg purified antibody with no preservative.
Detect and quantitate human collagen IV in serum, buffered solution, and cell culture supernatants using a homogeneous AlphaLISA no-wash assay.
The effect of cryopreserved human placenta fragments (CPF) implantation on female rats reproductive system and its function in the period of late ontogenesis was experimentally investigated. The increase of number of growing and mature follicles is educed twice, yellow bodies - in 1,8 time as compared to old falsely-operated females. There was a decline of index of apoptosis of cellular elements of ovaries, to the absorbancy of luminescence of collagen type IV and increase of intensity of luminescence of endotheliocytes that expressed receptors to endothelin- 1. After implantation of CPF of uterus on gravimetric coefficients were similar to such for young females. For the females of basic experimental group the decline of absorbancy of fluorescence of deoxyribonucleotides was observed in the nucleus of epitheliocytes and increase of absorbancy of fluorescence of ribonucleoproteins in the cytoplasm of cells of uteruses, that is the sign of increase of their functional activity, as compared to ...
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Collagen is a protein that naturally occurs in our bodies that is crucial to youthful-looking skin. Our collagen levels begin to deplete naturally after the age of 20. After that, we produce about 1% less collagen every year, which causes loss of elasticity, wrinkles, and thinner more fragile skin. The good news is, th
I recently presented the case of a middle-aged patient with ESRD secondary to Goodpasture syndrome. She presented with AKI 3 months after a kidney transplant. Her creatinine had normalized to 0.9mg/dl post-transplant. However, over the next few months…. ...
Collagen is one of the vital proteins your skin needs to maintain plumpness, radiance, and fight signs of ageing. Read on for the best ways to boost your collagen levels.
View Notes - Explicacion problema IV Sesion Colab Semaf-1 from SISTEMAS O 1 at ITESM. Problema IV Sesin Colaborativa de Semforos Problema del Productor Consumidor con Buffer
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