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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagen and elastin, the major structural components of blood vessels, have a very low turnover. In disease, this rate may be increased and an elevation of the tissue concentration of the soluble degradation fragments might be anticipated. In this preliminary study the concentration of extractable collagen and elastin in the aorta and pulmonary artery of eight human subjects postmortem was determined. The proportion of pulmonary artery collagen and elastin that was soluble was generally either equal to or greater than that in the abdominal aorta. The fraction of collagen that was salt extractable was larger than the soluble elastin fraction.
Exp Mol Pathol 1991 Aug
PMID:Salt-soluble collagen and elastin in the human aorta and pulmonary artery. 188 67

The myocardium consists of a muscle fibre array surrounded and interspersed by a network of connective tissue, principally collagen, which maintains the functional integrity of the heart. Changes in collagen composition may therefore contribute to altered ventricular function. Collagen composition was examined in cardiac tissue from 15 patients undergoing orthotopic cardiac transplantation. Of these, 10 had severely impaired left ventricular function due to coronary artery disease. The remaining five had dilated cardiomyopathy. Normal heart tissue was taken at autopsy from 25 patients who died of causes unrelated to cardiovascular disease. Left ventricular collagen concentration, estimated from hydroxyproline levels, increased from 48.6 +/- 4.1 mg/g dry weight of tissue in the control group to 95.3 +/- 9.7 mg/g (P less than 0.01) in patients with dilated cardiomyopathy and to 63.5 +/- 9.8 mg/g in the coronary artery disease group. This increase was attributable to an increase in absolute concentrations of both type I and III collagen, determined by separation of cyanogen bromide peptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis. However, there was a significant decrease in the proportion of type III collagen (compared with type I plus III) from 41.8 +/- 1.1% in controls, to 34.6 +/- 1.5% (P less than 0.01) in the coronary artery disease group and 35.8 +/- 2.8% (P less than 0.05) in the dilated cardiomyopathy group. These results suggest that excessive collagen production, with a preponderance of type I, occurs in these forms of myocardial disease, indicative of a remodelling of the collagen matrix, which, by increasing passive myocardial stiffness may contribute to impaired heart function seen in these groups of patients.
J Mol Cell Cardiol 1990 Oct
PMID:Enhanced deposition of predominantly type I collagen in myocardial disease. 209 38

The exon structure of the collagen IV gene provides a striking example for collagen evolution and the role of introns in gene evolution. Collagen IV, a major component of basement membranes, differs from the fibrillar collagens in that it contains numerous interruptions in the triple helical Gly-X-Y repeat domain. We have characterized all 47 exons in the mouse alpha 2(IV) collagen gene and find two 36-, two 45-, and one 54-bp exons as well as one 99- and three 108-bp exons encoding the Gly-X-Y repeat sequence. All these exons sizes are also found in the fibrillar collagen genes. Strikingly, of the 24 interruption sequences present in the alpha 2-chain of mouse collagen IV, 11 are encoded at the exon/intron borders of the gene, part of one interruption sequence is encoded by an exon of its own, and the remaining interruptions are encoded within the body of exons. In such "fusion exons" the Gly-X-Y encoding domain is also derived from 36-, 45-, or 54-bp sequence elements. These data support the idea that collagen IV genes evolved from a primordial 54-bp coding unit. We furthermore interpret these data to suggest that the interruption sequences in collagen IV may have evolved from introns, presumably by inactivation of splice site signals, following which intronic sequences could have been recruited into exons. We speculated that this mechanism could provide a role for introns in gene evolution in general.
J Mol Evol 1990 Jun
PMID:Evolution of collagen IV genes from a 54-base pair exon: a role for introns in gene evolution. 211 27

The effects of recombinant human interleukin-1 alpha (IL-1) on procollagen gene expression were examined in the clonal mouse osteoblastic cell line MC3T3-E1. Cells were grown in Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum and 50 micrograms/ml ascorbic acid. Collagen synthesis was assessed as [3H]proline incorporation into collagenase-digestible protein (CDP). Procollagen mRNA levels were determined by Northern blot analysis using a 32P-labeled alpha 1(I) cDNA. Transcription rates were determined by nuclear run-off assay. IL-1 at 1-1000 pg/ml caused a concentration-dependent inhibition of CDP, which was maximally reduced by 75-80%, and a parallel reduction of procollagen alpha 1(I) mRNA levels. The effects of IL-1 were mimicked by the tumor promoter phorbol 12-myristate 13-acetate (PMA) at 1-100 nM, which inhibited CDP and reduced procollagen alpha 1(I) mRNA levels to a similar extent. The effects of IL-1 and PMA were independent of prostaglandin production, since indomethacin did not alter the inhibitory effect of either agent on CDP. Neither IL-1 (up to 10 ng/ml) nor PMA (100 nM) affected adenylate cyclase activity, while forskolin (10 microM), PTH (10 nM) and prostaglandin E2 (1 microM) stimulated adenylate cyclase activity 3- to 5-fold. However, forskolin (10 microM) and (Bu)2cAMP (100 microM) failed to alter CDP or procollagen alpha 1(I) mRNA levels. IL-1 (1 ng/ml) and PMA (100 nM) reduced transcription of the alpha 1(I) procollagen gene by 70% and 80%, respectively, while alpha 2(I) transcription was decreased by 59% and 53%. Neither IL-1 nor PMA affected transcription of the beta-actin or beta-tubulin genes.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Feb
PMID:Interleukin-1 alpha and phorbol ester inhibit collagen synthesis in osteoblastic MC3T3-E1 cells by a transcriptional mechanism. 232 98

The assembly of type I collagen and type I pN-collagen was studied in vitro using a system for generating these molecules enzymatically from their immediate biosynthetic precursors. Collagen generated by C-proteinase digestion of pC-collagen formed D-periodically banded fibrils that were essentially cylindrical (i.e. circular in cross-section). In contrast, pN-collagen generated by C-proteinase digestion of procollagen formed thin, sheet-like structures that were axially D-periodic in longitudinal section, of varying lateral widths (up to several microns) and uniform in thickness (approximately 8 nm). Mixtures of collagen and pN-collagen assembled to form a variety of pleomorphic fibrils. With increasing pN-collagen content, fibril cross-sections were progressively distorted from circular to lobulated to thin and branched structures. Some of these structures were similar to fibrils observed in certain heritable disorders of connective tissue where N-terminal procollagen processing is defective. The observations are considered in terms of the hypothesis that the N-propeptides are preferentially located on the surface of a growing assembly. The implications for normal diameter control of collagen fibrils in vivo are discussed.
J Mol Biol 1989 Nov 20
PMID:Pleomorphism in type I collagen fibrils produced by persistence of the procollagen N-propeptide. 260 Sep 69

Collagens are a structurally and functionally heterogenous group of proteins encoded by a family of genes that share evolutionary history. Collagen gene expression is regulated both in developmental, tissue-specific manners as well as in response to a variety of biologic and pharmacologic inducers. In the present review we have attempted to synthesize a conceptual overview of the available information from studies aimed at deciphering the molecular mechanisms of collagen gene expression. We have chosen to focus our discussion mainly, although not exclusively, to observations relating to type I collagen gene for a number of practical reasons. The underlying theme that emerges from this survey of the literature is that the regulation of collagen gene expression is complex, utilizing transcriptional, posttranscriptional and translational mechanisms. Although the transcriptional control mechanisms that involve activation and modulation of collagen gene transcription by RNA polymerase II appear to predominate, preferential stabilization of collagen mRNAs and modulation of translational discrimination appear to play significant roles in the regulation of collagen biosynthesis under some physiological situations. Molecular organization of the regulatory regions of collagen genes reveal a mosaic of subdomains with overlapping sequence motifs, involved in positive and negative transcriptional regulation. The precise identity of the cis-acting subdomains of the promoter/enhancer-proximal DNA of collagen gene and how they interact with the trans-acting nuclear protein(s) have yet to be elucidated and will remain the focus of future studies.
Mol Cell Biochem 1989 Mar 16
PMID:Molecular mechanisms of collagen gene expression. 266 48

Changes in lung structure and collagen metabolism were studied at 1, 2, 3, 4, 6, and 8 weeks in a model of pulmonary fibrosis induced in rats with paraquat plus hyperoxia. Morphologic examination of the lungs revealed that the earliest lesions consisted of severe and irreversible endothelial and alveolar epithelial cell damage. Afterward, an inflammatory process took place, initially dominated by polymorphonuclear leukocytes and then by mononuclear cells, but with the constant presence of granulocytes. From the fourth week on there were fibroblast proliferation and a moderate increase of mast cells. In the early stages alveolitis was focal, but from the second week the lungs were diffusely affected with severe distortion of the architecture. Collagen content was moderately increased in the first 2 weeks and then showed a progressive increment until the end of the experiment. Collagen synthesis was significantly elevated from the fourth week, coinciding with interstitial fibroblast proliferation, although there were some animals that showed increased collagen production from the first week. Collagenolytic activity occurred in 3 stages: at 2 weeks there was increased collagen degradation, at 3, 4, and 6 weeks the values showed a trimodal behavior, and at 8 weeks almost all experimental rats presented an important decrease of collagenolysis. Thus, the development of lung fibrosis was associated first with increased rates of collagen synthesis and later with a decrease of collagen degradation.
Exp Mol Pathol 1989 Apr
PMID:Experimental pulmonary fibrosis induced by paraquat plus oxygen in rats: a morphologic and biochemical sequential study. 270 80

Collagen is the most abundant protein in the animal world and a principal component, of the extracellular matrix of tissues. Type I collagen is composed of two alpha 1 chains and one alpha 2 chain. The human alpha 2(I) locus (COL1A2) has been assigned to human chromosome 7q21.3-q22.1. Here, we report the mapping of its murine counterpart Colla-2 to mouse chromosome 6 (MMU6) by Southern blotting using somatic cell hybrids. This result disagrees with the previously reported mapping of Colla-2 to MMU16 by immunochemical techniques. Our results are supported by comparative mapping data showing conserved homology between regions of human chromosome 7 and mouse chromosome 6.
Somat Cell Mol Genet 1989 Sep
PMID:Gene for alpha 2(I) collagen is on mouse chromosome 6 not 16. 278 18

Acute local gamma irradiation of porcine skin induces, as in human skin, an extensive and mutilating sclerosis characterized by continuous expansion of the fibrosis invading the adjacent muscle and by accumulation of the macromolecular components of the extracellular matrix. Collagen synthesis, content, and types were studied in the presence of heparin fragments (100 micrograms/10(6) cells) in the culture medium, by measuring the incorporation of the radiolabeled precursor [3H]proline into confluent primary cultures of porcine fibroblasts obtained from normal and irradiated fibrotic dermis. Enhancement in collagen biosynthesis and deposition and preferential increase in collagen type III synthesis were observed in fibrotic fibroblast cultures when compared to those in normal dermis fibroblasts. The total collagen synthesis and the rate of collagen hydroxylation appear unmodified by heparin fragments both in normal and in fibrotic fibroblast cultures. But heparin fragments induce a 10- and 2-fold decrease, respectively, in collagen type III and type V syntheses by fibrosis fibroblasts. As only minor effects upon collagen type III and V are observed in cultures of normal dermis fibroblasts, these results highly suggest that heparin fragments are capable of specifically modulating the collagen phenotype of fibroblasts derived from radiation-induced dermis fibrosis and thus are able to regulate the fibrotic process.
Exp Mol Pathol 1989 Oct
PMID:Heparin fragments modulate the collagen phenotype of fibroblasts from radiation-induced subcutaneous fibrosis. 280 67

Myocardial collagen and total protein synthesis were studied in normal, diabetic, and insulin-treated diabetic rats after a single intraperitoneal injection of L-[2,3-3H]proline as a radioisotopic precursor. The incorporation of tritiated proline into myocardial protein was regarded as a measure of total protein synthesis and the incorporation into hydroxyproline as indicative of myocardial collagen synthesis. Both total protein and collagen synthesis were found to be significantly lower in diabetic rats. This was associated with decreased degradation of both total protein and collagen in diabetic rats, as suggested by prolonged turnover times. Collagen content was also found to be increased in diabetic myocardium. Early insulin therapy with normalization of blood sugars in diabetic rats returned myocardial collagen metabolism to normal. This suggests that maintenance of euglycemia in diabetic rats is necessary to prevent abnormal myocardial collagen metabolism.
Exp Mol Pathol 1988 Apr
PMID:Collagen metabolism in the myocardium of normal and diabetic rats. 296 30


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