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Query: UNIPROT:P06889 (Mol)
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Collagens are extracellular matrix proteins that play important structural roles in many tissues and organs. Thirteen types of collagen, the products of 23 genes, have been described. Most of the collagen genes are developmentally regulated; a given tissue or cell type expresses only a subset of the collagen genes. Type I collagen, the most abundant protein in vertebrate connective tissues, is produced by most cells of mesenchymal origin except hyaline cartilage. Each tissue or cell type expresses the type I collagen genes at a characteristic rate. Maintenance of the normal synthetic rate appears to be important for preservation of normal tissue structure and function. Fibrotic lesions are characterized by increased production of type I collagen. The mechanisms that determine both the normal tissue-specific pattern of type I collagen gene expression and the elevated expression in fibrosis are complex. Both transcriptional and post-transcriptional mechanisms have been described, with modulation of mRNA stability being perhaps the most important post-transcriptional mechanism. Several sequences have been identified in the promoters of the type I collagen genes which are required for transcriptional activity; in addition, transcriptional enhances have been identified within the first introns of the genes. Type I collagen gene expression is also regulated both positively and negatively by a variety of exogenous factors, including inflammatory response mediators. The specific combination of such exogenous factors available in a given tissue probably determines the net rate at which the genes are expressed.
Am J Respir Cell Mol Biol 1989 Sep
PMID:Collagen gene expression. 269 11

Previous studies investigating the cellular origins of several collagens in young adult rat hearts (Eghbali et al., 1988) demonstrated that the mRNAs for types I and III collagen occurred in non-myocyte cells, mostly fibroblasts, whereas the mRNA for type IV collagen was observed in both myocytes and non-myocyte cells. In the present study, cellular localization of collagen mRNAs has been achieved by in situ hybridization in rat heart tissue and in isolated heart cells. Frozen tissue sections, isolated cardiomyocytes, cultured neonatal cardiomyocytes and fibroblasts were hybridized with DNA probes for type-specific collagens, actin, and myosin heavy chain. Silver grains were visualized by dark field imaging. In heart sections, types I and III mRNAs were observed predominantly adjacent to myocytes and in the interstitium, where fibroblasts are known to be present. In contrast, type IV collagen mRNA was identified both within the myocytes and the interstitium. In freshly isolated adult cardiomyocytes and in cultured neonatal cardiomyocytes, collagen type IV mRNA was observed but type I collagen mRNA was not. In cultured neonatal fibroblasts, both types IV and I collagen mRNAs were abundant.
J Mol Cell Cardiol 1989 Jan
PMID:Localization of types I, III and IV collagen mRNAs in rat heart cells by in situ hybridization. 271 64

Long-term synovial fibroblast cultures were exposed to interleukin 1 (IL-1) or prostaglandin E2 (PGE2). The normally spindle-shaped fibroblasts changed to stellate-shaped cells, resembling the HLA-DR-positive, collagenase-producing cells which are normally seen only in primary cultures from enzyme-digested rheumatoid synovial tissue. However, the IL-1- or PGE2-induced fibroblasts were not HLA-DR-positive. This suggests that these cell populations represent originally different cell lines or that the expression of HLA-DR antigens is not induced by the agents used. For further characterization of these stellate cells, the location of fibronectin and type I collagen was studied by specific antibodies and the pericellular coat around fibroblasts was visualized by the erythrocyte exclusion method. Both IL-1 and PGE2 treatments destroyed the intercellular fibronectin network. Type I collagen was detected as intracellular granules. The stellate fibroblasts were usually full of these granules in contrast to intact fibroblasts in which the number of collagen fluorescence granules varied greatly. The pericellular coat known to be formed mainly by hyaluronic acid was similar around spindle and stellate-shaped fibroblasts. Rheumatoid arthritis-derived fibroblasts did not differ from their non-rheumatoid counterparts in any of the experiments. The effect of IL-1 and PGE2 on fibroblasts simulates the interaction between mononuclear cells and fibroblasts in synovial stroma and also potentially the interactions between different cell types in synovial lining.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Connective tissue components in synovial fibroblast cultures exposed to interleukin 1 and prostaglandin E2. 287 May 82

The meridional X-ray diffraction pattern of wet rat tail tendon contains information about the one-dimensional structure, or axial projection of electron density distribution of the type I collagen fibril. Using synchrotron radiation we have determined the intensities of the first 50 meridional X-ray diffraction reflections. The approach of isomorphous addition with reagents, selected using criteria of chemical reactivity, which label at fewer sites than the stains used in previous studies was applied to phase these 50 reflections to produce a one-dimensional electron density distribution map of a single D-repeat of the collagen fibril. This method is not model-dependent and thus constitutes the first unambiguous determination of the meridional phases of type I collagen.
J Mol Biol 1989 Feb 20
PMID:Phasing the meridional diffraction pattern of type I collagen using isomorphous derivatives. 292 22

Human cDNA libraries were screened with a cDNA fragment presumably encoding the 3' terminus of a procollagen carboxyl propeptide not identifiable as types I, II, III, or IV by protein sequence or Northern blot hybridization. One clone contained a 1350-base pair insert coding in part for 55 uninterrupted Gly-X-Y triplets. Comparison with the amino acid composition of the COOH-terminal cyanogen bromide (CB) peptides of the alpha 1 and alpha 2 type V collagen chains showed similarity only to the alpha 2(V)CB fragment. To identify the NH2 terminus of the peptide designated by methionine, an additional isolate was sequenced and found to contain a Gly-Met-Pro triplet. Thirty-one amino acids from the NH2 terminus of the alpha 2(V)CB9 fragment were then determined by Edman degradation and found to be identical to those derived from the cDNA clone. The DNA sequence encoding part of the triple helical region establishes for the first time the partial structure of a type V collagen chain. Although comparison of residues 796-1020 of the alpha 2(V) collagenous region with alpha 1 (III), alpha 1(I), and alpha 2(I) shows strong conservation of charged positions, the latter three chains appear considerably more similar to each other than to alpha 2(V). A striking feature of the alpha 2(V) sequence between 918-944 is the absence of proline residues. In the analogous region of alpha 1(I) where this amino acid is also lacking, a flexible site in the rigid triple helical structure of type I collagen has been observed (Hofmann, H., Voss, T., Kuhn, K. and Engel, J. (1984) J. Mol. Biol. 172, 325-343).
 ...
PMID:Partial covalent structure of the human alpha 2 type V collagen chain. 298 98

We have analyzed the effects of transformation by Rous sarcoma virus on expression of types I and II collagen and fibronectin genes in vertebral chondrocytes and compared them with expression of these genes in skin fibroblasts. Transformed chondrocytes display a dramatically decreased amount of type II collagen RNA, which can account fully for the decreased synthetic rate of this protein. Paradoxically, these cells also display greatly increased amounts of type I collagen RNAs, which are translated efficiently in vitro, but not in the intact cells. We show here that the type I collagen RNAs in transformed chondrocytes are nearly indistinguishable from those found in skin fibroblasts, and that they clearly differ from the type I collagen RNAs found in normal chondrocytes. Transformed chondrocytes also display an increased amount of fibronectin RNAs, which can account fully for the increased synthetic rate of this protein. Thus, the effects of transformation by Rous sarcoma virus on type I collagen and fibronectin RNAs in chondrocytes are the opposite of those observed in fibroblasts, which display decreased amounts of these three RNAs. These data indicate that the effects of transformation on the genes encoding type I collagen and fibronectin must be modulated by host cell-specific factors. They also imply that the types I and II collagen genes may be regulated by different mechanisms, the type I genes being controlled at both transcriptional and posttranscriptional levels, and the type II gene being controlled primarily at the transcriptional level.
Mol Cell Biol 1985 May
PMID:Control of types I and II collagen and fibronectin gene expression in chondrocytes delineated by viral transformation. 298 70

Antibodies against collagen types III and VI have been localized by electron immunohistochemistry with two different techniques in normal rat uterus and kidney. Antibodies directed against two components of the extracellular matrix with known localization, laminin and type IV collagen, were used as controls for the specificity of the localization. The results demonstrate that types III and VI are found in the interstitium as fine (10- to 15-nm), beaded fibrils and filaments (6- to 10-nm), respectively. Both are often found associated with thick, crossbanded type I collagen fibers (30- to 35-nm) and occasionally associated with some basement membranes adjacent to the interstitium. Further, the findings suggest that collagens III and VI may connect the various components of the extracellular matrix, such as type I fibers with basement membranes and other structures, thus forming an integrated functional unit.
J Ultrastruct Mol Struct Res 1988 Aug
PMID:Comparative ultrastructural localization of collagen types III, IV, VI and laminin in rat uterus and kidney. 322 77

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited diseases of connective tissue manifested primarily by excessive fracturing of bone but associated with other abnormalities such as blue sclera, thin skin, herniae, ligamentous laxity, reduced stature and hearing loss. We report here molecular studies on a patient with the mild, dominantly inherited, variety of OI (OI type I) previously shown (Nicholls et al., 1984) to be heterozygous for an abnormal alpha 1(I) chain of type I collagen which contained cysteine near the carboxyl terminus (Steinmann et al., 1986). The cognate alpha 1(I) mRNA region was selected for generation of cDNAs which were subsequently amplified by the polymerase chain reaction (PCR), cloned and sequenced. Two sequences were obtained, one of which corresponded to the normal allele, and the other of which harbored a G to T transversion and resulted in a cysteine for glycine substitution. This is the first single amino acid substitution found in type I OI. Surprisingly, the mutation occurs just outside the triple-helical region of the alpha 1(I) chain, a result that accounts for the strikingly different phenotypic and molecular consequences of this mutation as compared with similar cysteine for glycine substitutions within the same region. The PCR appears to be a useful approach for elucidation of structural mutations in collagen chains.
Mol Biol Med 1988 Dec
PMID:A cysteine for glycine substitution at position 1017 in an alpha 1(I) chain of type I collagen in a patient with mild dominantly inherited osteogenesis imperfecta. 324 12

Six months after acute local gamma irradiation of the pig skin and adjacent muscle, the muscular tissue is replaced by a large mutilating and proliferative fibrosis deliminated by a perifibrotic inflammatory zone. The content and biosynthesis of collagen and noncollagenous proteins were studied in both fibrotic and perifibrotic zones after incubation of the biopsies with [14C]proline or [35S]methionine for 24 hr. Cells of perifibrotic and fibrotic regions synthesize about 10 times more proteins than those in the nonirradiated muscle. When compared to normal muscle tissue, our results indicate an important increase in collagen content and biosynthesis in fibrotic tissue. The increase in collagen biosynthesis in the irradiated tissue is more pronounced for type III collagen than for type I collagen. Biosynthesis of type III and type I collagens increases 20- and 10-fold, respectively, compared to the normal muscle. Type I to III collagen ratio in irradiated tissue decreases from 2.3 in normal tissue to 1.1 in fibrotic tissue. Histological examination of the biopsies as well as the protein pattern by polyacrylamide gel electrophoresis show striking differences in the perifibrotic and fibrotic areas as compared to the normal muscular tissue with a progressive disappearance of the myotubes replaced by a dense sclerotic tissue. The results indicate that the perifibrotic inflammatory area is engaged in a remodeling process and that the fibrotic tissue remains active in the neosynthesis of the extracellular matrix macromolecules with a high proportion of type III collagen. This high biosynthetic activity of the irradiated tissue may explain the pseudosarcomatous character of the radiation-induced lesions.
Exp Mol Pathol 1988 Jun
PMID:Modification of collagen and noncollagenous proteins in radiation-induced muscular fibrosis. 337 53

Previous studies of the X-ray diffraction pattern of the crystalline regions of type I collagen fibrils yielded information on the unit cell parameters and also the orientation of the pseudo-hexagonally packed molecular segments in the overlap region. The absence of Bragg reflections at high angles attributable to the molecular segments in the gap region led to the suggestion that these segments were more mobile than those in the overlap region. We report a study of the low-angle Bragg reflections in a search for information about the nature of the orientation and packing of the molecular segments in the gap region. We conclude that the (m = 0, n = 0) helix layer plane of the molecular segments in the overlap region makes little or no contribution to the Bragg reflections at low angles, and identify three possible origins for the observed low-angle reflections in the electron density contrast associated with: (1) the "hole" created by the missing molecular segment in the gap region; (2) the telopeptides; or (3) the axial regularities in amino acid residues of a particular type, with periodicities of D/5 or D/6. Sufficient information is available to investigate the first two of these possibilities, and the results obtained suggest specific arrangements for the molecular segments in the overlap and gap regions, and specific connectivities between the molecular segments in successive overlap regions. In addition, we have examined the amino acid sequence and identified features related to the mobility of the molecular segments in the gap region and to the regions where it is thought that molecules are kinked.
J Mol Biol 1987 Jan 05
PMID:Molecular packing in type I collagen fibrils. 358 15


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