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Results for “Collagen Type VI”

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At least 19 recordsLinked to original sources

PubMed1991

Human bone contains type III collagen, type VI collagen, and fibrillin: type III collagen is present on specific fibers that may mediate attachment of tendons, ligaments, and periosteum to calcified bone cortex.

We evaluated the distribution of Type III collagen, Type VI collagen, and fibrillin in human bone, using monoclonal antibodies (MAb) of proven specificity. All three molecules are present in developing and remodeling bone. Type III collagen is present in discrete fiber bundles throughout the bone cortex but is concentrated at the Haversian canal surface and in the fibers at the bone-periosteal interface. The collagen fibrils in these bundles are of uniform diameter. Type III-containing collagen fibers are detected at all ages examined, from 30 fetal weeks to 80 years. Type VI collagen is present in fetal bone in discrete fibrils separate from Type III collagen, and becomes restricted to the margins of bone cells and the bone surface by 7 years. The distribution of fibrillin resembles that of Type III collagen in the fetus, but at 7 years is absent from the interior of the cortex except for the canaliculi and cement lines, and remains concentrated in discrete fibers at the bone surface.

Adult↗

PubMed1995

Attachment of articular cartilage chondrocytes to the tissue form of type VI collagen.

Type VI collagen is composed of a short triple helix rich in RGD sequences with globular domains at each extremity of the helix. Disulfide-bonded tetramers of the monomeric molecule associate non-covalently to form networks of microfibrils in connective tissues, including cartilage. The disulfide-bonded tetramer can be extracted with 6 M guanidine HCl and purified without pepsin digestion and is referred to here as the tissue form of type VI collagen. Type VI collagen in mature articular cartilage appears to be concentrated pericellularly. We undertook a systematic investigation using solid phase assays to establish the nature of the attachment of bovine articular cartilage chondrocytes to the intact, tissue form of bovine type VI collagen. The tissue form of type VI collagen was extracted from bovine meniscus cartilage with 6 M guanidine HCl and purified by polyethylene glycol precipitation. When equal molar quantities were coated on microwells, the tissue form of type VI collagen attached more cells than the pepsin-digested form of the molecule that lacked the globular domains. The attachment to the intact, tissue form was dose-dependent and saturable and was not inhibited by heparin or type II collagen. A linear GRGDSP peptide failed to inhibit attachment of the chondrocytes to the intact, tissue or pepsin-digested forms of type VI collagen, but totally inhibited the interaction when the intact molecule was reduced and alkylated. In contrast, a cyclic C*GRGDSPC* peptide inhibited attachment to the tissue form of type VI collagen, but not to fibronectin. The attachment had a metal ion dependence that could be satisfied by MnCl2, slightly less by MgCl2, but not at all by CaCl2. A direct interaction between the tissue form of type VI collagen and a chondrocyte cell surface receptor or receptors is a structural feature of the pericellular matrix in cartilage.

Amino Acid Sequence↗

PubMed1995

[Tissue localization and possible function of type VI collagen].

Type VI collagen was once considered a minor collagen, but now it is known as a major component of the extracellular matrices of most tissues. Type VI collagen tetramers aggregate into beaded filaments with repeats of approximately 100 nm, and the beaded filaments align laterally to form type VI collagen periodic fibrils by incubation with acidic ATP solution. Polyanionic ATP could cause lateral alignment of type VI collagen beaded filaments. Since the periodic structure is observable by transmission electron microscopy, we can examine the tissue distribution of type VI collagen by ATP treatment. Moreover, the interaction of type VI collagen with other extracellular matrix components can be examined by combining ruthenium red (RR) staining, which specifically interacts with tissue glycosaminoglycans (GAGs), with the ATP treatment. I here describe the localization and possible function of type VI collagen examined in our laboratory. After ATP incubation, numerous type VI collagen periodic fibrils appeared closely associated with striated collagen fibrils (mouse cornea and fibrous layer of mandibular condyle), with trophoblastic and endothelial basal lamina (human placenta), or with cell surface of fibroblasts (mouse tendon) and synovial cells (mouse synovium). The dark bands of the type VI collagen periodic fibrils were stained by RR, indicating the association of proteoglycans (PGs)/GAGs with this collagen. If the mouse corneal tissue was digested with chondroitinase ABC or testicular hyaluronidase prior to ATP treatment, type VI collagens were segregated to form periodic structures apart from striated collagen fibrils. In the mouse mandibular condyle, hyaluronidase digestion before ATP treatment caused unmasking of type VI collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1985

The platelet reactivity of collagen type VI.

Collagen type VI in native (undenatured or triple-helical) form has been shown, like collagen types I-V, alpha 1(I) trimer and alpha 2(I) trimer, to possess platelet reactivity provided that essential quaternary structural needs are first satisfied. Thus platelet aggregation was induced by the collagenous domain of collagen type VI, isolated free of the non-collagenous elements, when this entity was presented to platelets in fibrillar form. This implies that platelet recognition sites in collagen type VI are located in the collagenous sequence of the molecule. Aggregation of platelets was also induced, although a higher concentration was required, by the intact, "parent" collagen following its polymerisation by random association of molecules with the aid of a cross-linking agent (glutaraldehyde) to yield an amorphous polymer. This permits the suggestion that the more ordered molecular assembly of collagen type VI thought to occur in vivo, to yield a microfibrillar form, is likely to be associated with significant platelet reactivity. Our results support the notion that any collagenous species may be reactive towards platelets provided that essential tertiary and quaternary structural requirements are met and in this sense, therefore, they favour more the idea of multiple platelet-reactive sites in collagen of relatively low structural specificity and low affinity.

Animals↗

PubMed1987

Isolation of cDNA clones corresponding to the Mr = 150,000 subunit of chick type VI collagen.

Type VI collagen is a disulfide-bonded protein with an unusual structure in that the molecule contains three short triple-helical domains and very extended non-collagenous regions. The molecule is a heterotrimer composed in the chick of two polypeptides of similar apparent size in SDS-PAGE (Mr = 140- and 150,000) but different structure, and a third component that is much larger (Mr = 260,000) than the other two chains. We report here on the isolation of several overlapping cDNA clones from a chicken aorta mRNA expression library in the plasmid vector pEX1. Antibodies affinity purified onto the fusion proteins recognized the chick type VI collagen Mr = 150,000 subunit. Northern blots using the cDNA inserts from the above clones revealed a single RNA species of about 4,600 nucleotides sufficient to code for a protein with the size of the Mr = 150,000 subunit.

Animals↗

PubMed1988

Cloning and chromosomal localization of human genes encoding the three chains of type VI collagen.

Type VI collagen is a heterotrimer composed of three polypeptide chains, alpha 1(VI), alpha 2(VI), and alpha 3(VI). By immunological screening of an expression cDNA library, human cDNAs specific for each chain were isolated and characterized. Major mRNA species encoding these chains have a size of 4.2 kb (alpha 1), 3.5 kb (alpha 2), and 8.5 kb (alpha 3). The cDNA clones were also used to map the genes on human chromosomes by somatic cell hybrid analysis and in situ hybridization. The alpha 1 (VI) and alpha 2(VI) collagen genes were both located on chromosome 21, in band q223. This represents a third example of a possible physical proximity of two collagen loci. The alpha 3(VI) collagen gene was localized to chromosome 2, in the region 2q37. The alpha 3(VI) collagen gene is the fifth extracellular matrix gene to be localized to 2q, as four other extracellular matrix genes--i.e., the alpha 1(III) and alpha 2(V) collagen genes, the elastin gene, and the fibronectin gene--have been previously mapped to the distal region of the long arm of chromosome 2.

Amino Acid Sequence↗

PubMed1984

Ehlers-Danlos syndrome type VI: collagen type specificity of defective lysyl hydroxylation in various tissues.

The Ehlers-Danlos syndrome type VI is an inherited disorder of collagen metabolism characterized by a defective lysyl hydroxylase. The resulting lack of hydroxylysine has been found in several connective tissues, all of which show varying degrees of clinical symptoms. In the present study, collagen was isolated from different connective tissues and the degree of hydroxylation of lysyl residues was determined. Subsequently, collagen types I, II, III, IV, and V have been prepared from a number of tissues. Insufficient hydroxylation of lysyl residues was found in type I and type III collagen, whereas types II, IV, and V showed normal amounts of hydroxylysine. The expression of the defect, even for type I and type III collagen, varied widely from one tissue to another. A complete lack of hydroxylysine was observed in skin, while it was less pronounced in tissues such as bone, tendon, lung, or kidney. The data suggest the presence of several isoenzymes having varying affinities to the different collagen types.

Adult↗

PubMed1995

Reduced thrombogenicity of type VI collagen as compared to type I collagen.

Type VI collagen has been recently identified as a major constituent of vascular subendothelium where it serves as a binding site for von Willebrand factor. The present study compares the functional characteristics of type VI collagen with those of type I collagen with respect to platelet aggregating and secretory activities. The differences between the two collagens in platelet aggregation and serotonin and beta-thromboglobulin release were found to be highly significant (p < 0.001, p < 0.0007, p < 0.005 respectively). Our results indicate that under in vitro conditions, type VI collagen stimulates a significantly lesser platelet activation and aggregation response than collagen I, suggesting that type VI collagen may play a role in vivo to limit the platelet thrombotic response following injury to the vascular subendothelium.

Collagen↗

PubMed1997

Type VI collagen anchors endothelial basement membranes by interacting with type IV collagen.

Type VI collagen filaments are found associated with interstitial collagen fibers, around cells, and in contact with endothelial basement membranes. To identify type VI collagen binding proteins, the amino-terminal domains of the alpha1(VI) and alpha2(VI) chains and a part of the carboxyl-terminal domain of the alpha3(VI) chain were used as bait in a yeast two-hybrid system to screen a human placenta library. Eight persistently positive clones were identified, two coding the known matrix proteins fibronectin and basement membrane type IV collagen and the rest coding new proteins. The amino-terminal domain of alpha1(VI) was shown to interact with the carboxyl-terminal globular domain of type IV collagen. The specificity of this interaction was further studied using the yeast two-hybrid system in a one-on-one format and confirmed by using isolated protein domains in immunoprecipitation, affinity blots, and enzyme-linked immunosorbent assay-based binding studies. Co-distribution of type VI and type IV collagens in human muscle was demonstrated using double labeling immunofluorescent microscopy and immunoelectron microscopy. The strong interaction of type VI collagen filaments with basement membrane collagen provided a possible molecular pathogenesis for the heritable disorder Bethlem myopathy.

Adult↗

PubMed1994

Patterns of type VI collagen compared to types I, III and V collagen in human embryonic and fetal skin and in fetal skin-derived cell cultures.

The distribution of type VI collagen was examined in human embryonic and fetal skin and in cultured cells and matrix from this tissue. Frozen sections were immunolabeled with primary antibodies against type VI collagen and types I, III or V collagen, and processed further for fluorescence microscopy and immunoelectron microscopy. At 6 weeks estimated gestational age (EGA), type VI collagen was identified by positive fluorescence and by immunogold staining of filaments and fibers beneath the dermal-epidermal junction (DEJ), weaker fluorescence in the fine matrix of the dermis, and stronger fluorescence in the subcutis. At progressive stages of gestation, immunolabeling for type VI collagen increased in the dermis in parallel with increased deposition of types I and III collagen. By 15 weeks EGA, type VI collagen stained intensely throughout the dermis. At 13 weeks EGA, type VI collagen appeared diminished from the growing tips of invaginating hair buds, but as the hair peg developed, type VI collagen accumulated in adnexal sheaths. Cell cultures were derived from fetal skin at 7.5 to 12 weeks EGA. In primary explant cultures containing both keratinocytes and fibroblasts, mats of type V collagen were present beneath keratinocytes and associated with dense spots that co-labeled for both type VI and type V collagen. In passaged cultures of fibroblasts, individual cells with or without pretreatment with monensin were positive for type VI and/or types I, III or V collagen. Fibrous matrix that was labeled for type VI collagen was also immunopositive for type I or III collagen, while filamentous matrix that was type VI collagen positive tended to exclude types I and III collagen but in some areas to overlap with type V collagen. These findings support the hypothesis that type VI collagen present in both filamentous and fibrous matrix and networks of type VI collagen may serve as a fine scaffolding that facilitates the integration of types I and III collagen into developing fibrous matrix.

Antibodies, Monoclonal↗

PubMed1988

Monoclonal antibodies for the different chains of chick type VI collagen.

Avian type VI collagen is composed of three subunits of Mr 140,000, 150,000 and 260,000. Monoclonal antibodies were raised against type VI collagen isolated from chick embryo gizzard, and these antibodies were used to immunoprecipitate type VI collagen from metabolically labeled embryo cells. Several antibodies appeared to react with epitopes independent of glycosylation and hydroxylation processes. The antibody-binding sites were identified on the different chains by immunoblotting of total cell extracts. In addition, antibodies that recognized different epitopes on the Mr 260,000 subunit could be grouped in at least three different clusters by competitive inhibition radioimmunobinding assays.

Animals↗

PubMed1997

Clinical significance of serum 7S collagen and type VI collagen levels for the diagnosis of hepatic fibrosis.

OBJECTIVE: To measure serum 7S collagen (7S-C) and type VI collagen (VI-C) levels by radioimmunoassay (RIA) in Chinese patients with various liver disorders and in CCl4-treated SD rats, and to investigate the significance of the elevated levels of serum 7S-C and VI-C. METHODS: Serum 7S-C and VI-C levels were measured in 40 healthy control subjects, 168 patients with various liver disorders and non-hepatic diseases, and 52 CCl4-treated SD rats by using RIA which was developed in our hospital. RESULTS: Serum 7S-C and VI-C were significantly elevated in patients with chronic active hepatitis (CAH), liver cirrhosis (LC), hepatic cellular carcinoma (HCC) (P < 0.01 respectively), chronic persistent hepatitis (CPH), and some with non-hepatic diseases (P < 0.05). Serum 7S-C, serum laminin and hyaluronic acid were well correlated. Serum 7S-C and VI-C were not closely correlated. Both collagens were correlated with serum albumin/globulin ratio, aminotransferase and total bilirubin, not with alkaline phosphatase. In CCl4-treated SD rats, serum 7S collagen and type VI collagen levels were correlated with the degree of hepatic fibrosis. CONCLUSIONS: Serum 7S collagen and type VI collagen are useful markers for diagnosing liver fibrosis. And the combined measurement of IV-C, VI-C and other markers of connective tissue metabolism or biochemical data seems to provide additional information to predict progressive hepatic fibrosis.

Animals↗

PubMed1986

Type VI collagen is a major component of the human cornea.

Collagen type VI is shown to be present in the human cornea. This finding is based on comparative peptide mapping relative to type VI collagen isolated from placenta and on immunoblotting using antibodies specific for human type VI collagen. Scanning of polyacrylamide gels indicates that type VI collagen comprises as much as one quarter of the dry weight of the cornea. Indirect immunofluorescence shows this collagen to be distributed throughout the corneal stroma. Thus, type VI collagen must be considered a major component of the extracellular matrix of the human cornea.

Aged↗

PubMed1993

Monoclonal antibodies to type VI collagen demonstrate new tissue augmentation of a collagen-based biomaterial implant.

We developed a panel of highly specific monoclonal antibodies (MAb) to either human or dog collagen Type VI. Various degrees of species crossreactivities were found with ELISA and immunohistology. Because of these differentiating species specificities, which allowed distinction between the original donor collagen and newly formed host collagen, the MAb proved to be valuable tools in examination of explanted samples of an ovine composite vascular prosthesis retrieved from a canine model. With an MAb that reacts with dog but not sheep collagen Type VI, newly synthesized pockets of collagen Type VI could readily be detected within the prosthesis as early as 3 months after implantation. These areas were associated with regions of cell infiltration, presumably derived from the host. This association was also apparent in the newly formed intimal region of the prosthesis where only host cells were found. Another of the MAb, which was positive against human but not sheep collagen, was also used to demonstrate marked deposition of host collagen Type VI in a retrieved human sample of the prosthesis. In this case the antibody was able to detect collagen on a formalin-fixed tissue, which would broaden the scope of its use in clinical and pathological situations. Use of these novel antibody probes provides a rapid marker for new tissue augmentation of implanted biological devices which would be an indicator of the long-term performance of a prosthesis.

Animals↗

PubMedDate not supplied

Synovial extracellular matrix: partial characterization of matrix components and identification of type VI collagen molecular forms.

Alterations in the synovial extracellular matrix (ECM) in chronic inflammatory arthritis may affect synoviocyte adhesion and may be important in the regulation of pannus growth and invasion. Immunohistochemical examination of synovium has revealed enhanced deposition of fibronectin and collagen in interstitial areas consistent with expansion of the ECM in inflammatory arthritis. In order to functionally characterize the ECM of synovium, synovial extracellular matrix was purified from pannus removed at joint replacement surgery. A prominent 140 Kd 6M guanidine extractable component was found to mediate synoviocyte adhesion in a cell-blotting assay. This 140 Kd component was identified as a form of type VI collagen. Type VI collagen appears to be a significant component of synovial ECM.

Cell Adhesion Molecules↗

PubMed2000

[Expression of type VI collagen in arthrofibrosis. An immunohistochemical study].

Arthrofibrosis is a disabling complication after trauma and surgery due to massive connective tissue proliferation. The etiology and pathogenesis have never been fully understood. A strong immune response may lead to activation and proliferation of fibroblasts with excessive and disordered deposition of matrix proteins. In similar pathological conditions, like lung fibrosis or superficial fibromatoses with fibrotic transformation an increased expression of collagen type VI has been reported. We investigated fibrotic tissue samples taken from 18 patients (average age: 32.7 years), who underwent arthrolysis of the knee joint because of symptomatic arthrofibrosis following ligament injury. The mean interval between trauma and arthrolysis was 13.8 months (range 4-50 months). Tissue samples were taken from the infrapatellar fat pad and intercondylar connective tissue. All samples were stained with HE. The expression of type III and VI collagen was studied immunohistochemically using an immunoperoxidase method for light microscopic visualization. Histologic analysis from patients with arthrofibrosis showed a synovial hyperplasia with cell infiltration and vascular proliferation compared to synovial tissue samples from knee joints without any detectable pathology. Subsynovial an increased deposition of matrix proteins was visible. Type VI collagen was widely distributed as a network subsynovial and around capillary walls. Type III collagen showed a diffuse distribution. Arthrofibrotic tissue is, similar to pathological conditions with fibrotic transformation characterized by an increased expression of collagen type VI. Collagen type VI may play an important role in matrix homeostasis. It serves as an anchoring element between collagen fibers and as a cell binding structure.

Adolescent↗

PubMed1997

Microfibril-associated glycoprotein-1 (MAGP-1) binds to the pepsin-resistant domain of the alpha3(VI) chain of type VI collagen.

The interactions of type VI collagen have been investigated, using solid phase binding assays, with two components of the fibrillin-containing microfibrils, the elastin-binding protein, MAGP-1 and its structural relative MAGP-2. Both native and pepsin-treated forms of type VI collagen specifically bound to MAGP-1 but not to MAGP-2. Pepsin type VI collagen was shown to block the binding of MAGP-1 to native type VI collagen indicating that the major MAGP-1-binding site was in the triple-helical region of the molecule. MAGP-1 was found not to bind to collagens I, III, and V. Affinity blotting of pepsin-treated type VI collagen showed that MAGP-1 binding was specific for the collagenous domain of the alpha3(VI) chain. Decorin and biglycan were found not to inhibit the interaction of pepsin-treated type VI collagen with MAGP-1, indicating that its binding site on the collagen is not close to that for the proteoglycans. Reduction and alkylation of disulfide bonds in MAGP-1 did not destroy its type VI collagen-binding properties, indicating that the binding site was likely to be in the cysteine-free, N-terminal domain of MAGP-1. Interestingly, the interaction of MAGP-1 with type VI collagen was inhibited by tropoelastin, suggesting that the binding sites for tropoelastin and type VI collagen may be in the same domain of MAGP-1. A peptide, corresponding to amino acids 29-38 of MAGP-1, was found to inhibit the interactions of MAGP-1 with type VI collagen and tropoelastin. The results suggest that the peptide may contain the binding sequences for both type VI collagen and tropoelastin, and thus that these two proteins may share the same binding site on MAGP-1. The interactions of MAGP-1 with type VI collagen and tropoelastin were both determined to be of moderately high affinity, with Kd values of 5.6 x 10(-7) M and 2.6 x 10(-7) M, respectively. The findings indicate that MAGP-1 may mediate a molecular interaction between type VI collagen microfibrils and fibrillin-containing microfibrils, structures which are often found in close proximity to each other in a wide range of extracellular matrices.

Amino Acid Sequence↗

PubMed1992

Corneal cell-matrix interactions: type VI collagen promotes adhesion and spreading of corneal fibroblasts.

Type VI collagen is a nonfibrillar collagen present as a network throughout the chick secondary stroma. Immunolocalization of type VI collagen both in the chick corneal stroma and in other systems demonstrates that type VI collagen is present associated with cells and between striated fibrils. We hypothesize that type VI collagen may function in cell-matrix interactions important in corneal development. To examine this possibility, we have isolated and characterized bovine corneal type VI collagen and determined that the chain composition and morphology of type VI collagen isolated from cornea is similar to that isolated from other sources. The tissue form of type VI collagen was localized to filaments forming a network around fibrils and close to corneal fibroblasts. We then analyzed relative attachment and spreading on type VI collagen as compared to the other collagens present in the secondary stroma, and found that although corneal fibroblasts attach equally well to type VI and type I collagen, cells spread to a much greater extent on type VI collagen. Although corneal fibroblasts do have an RGD-dependent receptor which functions during adhesion to fibronectin, attachment to type VI collagen is RGD-independent unless the molecule is denatured. Blocking of the RGD-dependent receptor with soluble RGD peptides results in no change in attachment or spreading. These data imply a role for type VI collagen in cell-matrix interactions during corneal stroma development.

Amino Acid Sequence↗