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

Percutaneous transluminal coronary angioplasty is associated with intimal hyperplasia and extracellular matrix deposition of collagen, leading to restenosis in a significant number of cases. The purpose of the present study was to determine the effects of balloon angioplasty on extracellular matrix collagen content and collagenase activity in a porcine coronary artery restenosis model 6 weeks following balloon injury. We tested the hypothesis that in balloon-injured arteries the neointimal extracellular matrix was characterized by increased collagen content and decreased metalloproteinase activity relative to non-injured arteries. Male miniswine maintained on a high cholesterol diet underwent cardiac catheterization and double balloon injury to the right and left circumflex coronary arteries. The coronary arteries were either pressure-perfusion-fixed and prepared for histological examination, or dissected free of adventitia for further collagen and matrix metalloproteinase studies. Collagen synthesis in balloon-injured coronary arteries was compared to non-injured arteries using Northern blot analysis and histochemical stains. Comparative studies on differences between balloon-injured and non-balloon-injured arterial matrix metalloproteinase activity were done using zymography. Balloon angioplasty arterial injury resulted in a significant increase in type I collagen mRNA expression, with increased collagen deposition in the extracellular matrix. In contrast, matrix metalloproteinase activity was markedly decreased. The results suggest that the increased neointimal extracellular matrix observed late in the injury response may be due to not only increased collagen synthesis, but also reduced degradation. The failure to achieve a balance between the synthesis and degradation of extracellular matrix collagen could serve as an important mechanism responsible for restenosis.
J Mol Cell Cardiol 1996 Apr
PMID:Extracellular matrix collagen synthesis and degradation following coronary balloon angioplasty. 873 98

It is established that thyroxine-induced ventricular hypertrophy is associated with downregulation of collagen type I gene expression and increased collagen turnover in the ventricular tissue. The present study was undertaken to test the hypothesis that circulating thyroid hormones may have a regulatory impact on the biosynthesis of the collagen matrix in the heart. To this end, we determined collagen gene expression and deposition in the hearts of male and female Sprague-Dawley rats after surgical thyroidectomy. The serum levels of 3,3'5-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) in thyroidectomized and age/sex-matched sham-operated rats were determined by radioimmunoassay and fluorescence analysis of the serum, respectively. On day 14 post-surgery, the plasma levels of both T3 and T4 in thyroidectomized rats were decreased by greater than 85% compared with those in matching sham-operated control rats. At this time, Northern analysis of ventricular RNA from thyroidectomized rats showed a 160% (P = 0.0079) increase for pro alpha 1 (I) and a 43% increase (P = 0.0484) for pro alpha 2 (I) collagen mRNAs in the ventricular tissue of male rats compared with that in the heart of age-matched, sham-operated control rats. In the female rats, thyroidectomy led to 63% (P = 0.0469) increase in the abundance of pro alpha 1 (I) collagen and 50% (P = 0.034) increase for pro alpha 2 (I) collagen in ventricular tissue. At the protein level, the amount of collagen type I as determined by immuno-slot blotting of ventricular homogenates, was increased in the ventricular tissue of both male (131%, P = 0.0371) and female (108%, P = 0.0464) rats. Comparison of the changes in males v females showed relatively greater increases in the level of collagen type I mRNA and protein in ventricular tissue of thyroidectomized males. Of particular note, were the increases in the immunoreactive TGF-beta in ventricular tissue of thyroidectomized male and female rats which showed a pattern similar to that of changes in collagen type I. Immunofluorescent light microscopy of frozen heart sections, showed significant remodeling of the type I collagen fibers in the ventricular myocardium of thyroidectomized rats compared with age/sex-matched sham-operated rat heart. Together, these findings suggest that circulating thyroid hormones play a role in physiological regulation of collagen type I biosynthesis in the heart and this role may vary in males and females. They further suggest that normal production of collagen matrix in the heart may be dependent on the functional status of thyroid hormones.
J Mol Cell Cardiol 1996 Jan
PMID:Upregulation of collagen type I gene expression in the ventricular myocardium of thyroidectomized male and female rats. 874 12

We compared the expression of osteoblastic markers in cultured human cells isolated from fracture calluses of various histological states of development with that in cells from adult and fetal bone. Adult osteoblasts and all callus cells produced almost exclusively type I collagen, whereas fetal osteoblasts produced also considerable amounts of type III collagen in vitro. 1,25-Dihydroxyvitamin D3 induced the synthesis of osteocalcin in all bone and callus cells but to varying extents. Fetal bone cells and early-stage callus cells synthesized less than 10% the amount of osteocalcin produced by adult bone cells. Late-stage callus cells produced intermediate levels of osteocalcin. Fetal bone cells and early-stage callus cells responded to parathyroid hormone with a less pronounced increase in intracellular cAMP than did adult bone cells. Late-stage callus cells showed the best response to parathyroid hormone. The activity of alkaline phosphatase was highest in fetal bone cells. These observations show that cells isolated from fetal bone and from fracture callus tissues express a pattern of markers clearly relating them to the osteoblastic lineage. On the basis of the different patterns of osteoblastic markers expressed in vitro we conclude that functionally distinct subtypes of osteoblasts do exist in different mineralized tissues and at different developmental stages.
J Mol Med (Berl) 1995 Nov
PMID:Expression of osteoblastic markers in cultured human bone and fracture callus cells. 875 Nov 41

Oxygen radicals are induced under various pathologic conditions associated with neovascularization. Oxygen radicals modulate angiogenesis in cultured human microvascular endothelial cells by an unknown mechanism. Treatment of human microvascular endothelial cells for 15 min with 0.1 to 0.5 mM hydrogen peroxide (H2O2) or 100 U of tumor necrosis factor alpha per ml induced tubular morphogenesis in type I collagen gels. Gel shift assays with nuclear extracts demonstrated that H2O2 increases the binding activities of two transcription factors, NF-kappaB and AP-1, but not of Spl. Tumor necrosis factor alpha increased the binding activities of all three factors. A supershift assay with specific antibodies against JunB, JunD, and c-Jun (Jun family) showed that the antibody against c-Jun supershifted the AP-1 complex after H2O2 treatment. Coadministration of the antisense sequence of NF-kappaB inhibited H2O2-dependent tubular morphogenesis, and the antisense c-Jun oligonucleotide caused partial inhibition. The angiogenic factor responsible for H2O2-induced tubular morphogenesis was examined. Cellular mRNA levels of vascular endothelial growth factor and interleukin-8 (IL-8), but not those of transforming growth factor alpha, were increased after treatment with 0.5 mM H2O2. Coadministration of anti-IL-8 antibody inhibited tubular morphogenesis enhanced by H2O2, and IL-8 itself also enhanced the formation of tube-like structures. Treatment with antisense NF-kappaB oligonucleotide completely blocked H2O2-dependent IL-8 production by endothelial cells. The tubular morphogenesis of vascular endothelial cells after treatment with oxidative stimuli and its possible association with NF-kappaB and IL-8, is examined.
Mol Cell Biol 1996 Aug
PMID:Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. 875 23

Expression of type I collagen genes is highly regulated and becomes abnormal in various pathological conditions, from excessive collagen production in fibrotic diseases to their downregulation in transformed cells. Some inflammatory cytokines and other ligands, capable of eliciting intracellular phosphorylation, can profoundly alter collagen gene expression. We investigated the role of serine/threonine protein phosphatases (PP) in the regulation of collagen gene expression. Biosynthesis of the endogenous type I procollagen, and expression of Pro alpha 1(I) promoter-luciferase (Luc) constructs transfected in NIH3T3 fibroblasts, were evaluated in response to PP2A and PP1 inhibitor okadaic acid (OA) and exogenously expressed PP catalytic subunits. OA suppressed type I collagen gene expression as judged by reduced rates of protein synthesis, steady state levels of Pro alpha 1(I) collagen mRNA and expression of Luc driven by Pro alpha 1 (I) collagen promoter in OA-treated cells. Co-transfection of Pro alpha 1(I)-Luc with expression vectors containing PP2A, but not PP1, stimulated collagen promoter activity. These results strongly suggest that OA acts via PP2A-mediated dephosphorylation of an unidentified transcription factor(s) or cofactor(s) needed to activate Pro alpha 1(I) collagen promoter.
Mol Cell Biochem 1996 May 10
PMID:Okadaic acid-induced transcriptional downregulation of type I collagen gene expression is mediated by protein phosphatase 2A. 879 Dec 82

Fibroblasts from a 23 week old fetus affected with lethal (type II) osteogenesis imperfecta (OI) produced normal and abnormal type I procollagen molecules. The abnormal molecules were shown to contain pro alpha 1(I) chains in which the glycine at position 382 of the triple helical domain was substituted by arginine, as the result of a G-to-C transversion at nucleotide 1797 of the pro alpha (I) coding sequence. Also fibroblasts from the apparently normal father produced abnormal type I collagen but the overmodified alpha 1(I) chains tended to disappear with increasing passage number. We determined that the mutant allele accounted for approximately 36% of the COL1A1 alleles in the father's skin fibroblasts. Upon careful clinical reexamination, the man appeared to be very mildly affected with OI. The most plausible explanation for such a phenotypic variation is that the father is a mosaic for a mutation that is lethal in the heterozygous son. This finding confirms previous observations that somatic mosaicism for new dominant mutations is responsible for extreme intrafamilial variability and poses some caveats in genetic counselling.
Mol Cell Probes 1996 Jun
PMID:Intrafamilial variable expressivity of osteogenesis imperfecta due to mosaicism for a lethal G382R substitution in the COL1A1 gene. 879 76

The regulation of collagen gene expression by serotonin was investigated in rat uterine smooth muscle cells. Serotonin treatment of myometrial cells caused decreases of up to 10-fold in levels of type I collagen mRNA. Decreases in secreted type 1 collagen protein paralleled decreases in collagen mRNA. The effective half-life of collagen mRNA in serotonin-treated cells was approximately 1.7 days. Selective 5-HT2 receptor agonists mimicked the effects of serotonin, while the effects of serotonin were blocked by 5-HT2 antagonists. Nuclear run-on analysis showed that serotonin-dependent decreases in collagen mRNA are accompanied by decreased transcription. Progesterone analogs, which inhibit the serotonin-dependent activation of the gene for interstitial collagenase, had no effect on the ability of serotonin to decrease collagen mRNA. Conversely, the cell-permeable cAMP analog, 8-bromo-cAMP, mimicked the effects of serotonin on type I collagen mRNA and protein. Serotonin also decreased levels of the mRNAs for type III collagen and fibronectin, but had no effect on the mRNAs for type IV collagen. These results indicate that serotonin, previously shown to upregulate the interstitial collagenase gene, downregulates the gene for type I collagen and other extracellular matrix proteins, possibly by a novel mechanism of action downstream of 5-HT2 receptor binding.
Mol Cell Endocrinol 1996 Jul 01
PMID:Serotonin regulation of gene expression in uterine extracellular matrix: reciprocal effects on collagens and collagenase. 883 71

Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: alpha 1(V)2 alpha 2(V) or alpha 1(V) alpha 2(V) alpha 3(V). We report that genomic polymorphisms at the pro alpha 1(V) gene (COL5A1) locus cosegregated with the gravis form of Ehlers-Danlos syndrome (EDS) (type I) in a three generation family. Affected family members, who had classical features including joint hyperextensibility, fragile skin, and widened, atrophic scars, were heterozygous for a 4 bp deletion at positions from +3 to +6 of intron 65, which resulted in removal of exon 65 sequences from processed mRNAs. Since exon 65 encodes 78 residues of the carboxyl propeptide, the expected result of this mutation is reduced efficiency in incorporating mutant pro alpha 1(V) chains into type V collagen molecules and reduced type V collagen synthesis. These studies indicate that heterozygous mutations in COL5A1 can result in EDS type I. However, linkage studies in other EDS I families indicate the disorder is heterogeneous; linkage to both COL5A1 and COL5A2 was excluded in two other families with EDS I while a fourth family was concordant for linkage to COL5A1 (Z = 2.11; theta = 0.00).
Hum Mol Genet 1996 Nov
PMID:A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro alpha 1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I). 892

Of TGF-beta superfamily proteins, BMP-2 enhanced alkaline phosphatase (ALP) activity in cultured osteoblastic cells, MC3T3-E1, to the same level promoted by ascorbate, whereas TGF-beta s (beta 1, beta 2, beta 3) reduced ALP activity and altered cell morphology under the same conditions. Activin appeared to have no distinct effect on ALP synthesis. Ascorbate dependent increase in ALP synthesis was markedly stimulated in the presence of BMP-2. The synergistic effect of ascorbate on ALP synthesis was replaced by type I collagen coated on the culture dish. However, BMP-2 appeared not to bind to type I collagen. These findings indicate that BMP-2 acts directly on osteoblastic cells through its receptors and collagenous matrix can neither recruit BMP-2 nor modulate directly the action of BMP-2 in the pericellular area. Treatment of cells grown in ascorbate media with TGF-beta s decreased rapidly the cellular ALP activity indicating that TGF-beta s direct cells to the dedifferentiated stage.
Mol Cell Biochem 1996 Dec 06
PMID:Synergistic effect of BMP-2 and ascorbate on the phenotypic expression of osteoblastic MC3T3-E1 cells. 897 78

The purpose of our studies was to identify factors which regulate the composition of airway secretions produced by normal human tracheobronchial epithelial (NHTBE) cells. Individual factors were removed from the culture media of NHTBE cells grown in air-liquid interface (ALI) cultures (which support mucociliary differentiation) and the effects on mucin, lysozyme (LZ), and secretory leukocyte protease inhibitor (SLPI) secretion and gene expression were examined. Deletion of hydrocortisone, epinephrine, transferrin, or gentamycin-amphotericin from the media had no reproducible effects; deletion of insulin was incompatible with culture growth. We identified 3 factors, namely retinoic acid (RA), triiodothyronine (T3) and collagen gel substratum, which had a major impact on the profile of NHTBE secretions. Removal of RA from the media caused a drastic decrease in mucin secretion and a decrease in expression of the mucin genes MUC2 and MUC5AC.LZ and SLPI secretions were increased in these cultures. Paradoxically LZ mRNA was decreased, while SLPI mRNA levels were increased. Removal of T3 selectively increased mucin secretion, MUC2 gene expression was not affected, but MUC5AC mRNA levels reproducibly increased, suggesting that the expression of these two mucin genes is differentially regulated. LZ and SLPI secretion levels were not significantly affected by deletion of T3 from the culture media; however, LZ mRNA levels were increased in the absence of T3 while SLPI transcript levels were not affected. Omission of the attachment substratum, type I collagen gel, resulted in significant increases in all 3 secretory products. MUC2 and MUC5AC steady state mRNA levels were not consistently affected. In contrast LZ and SLPI gene expression were reproducibly increased. Our studies show that individual factors in the epithelial environment can regulate expression of specific secretory cell gene products in a highly selective manner.
Am J Respir Cell Mol Biol 1997 Jun
PMID:Regulation of the secretory phenotype of human airway epithelium by retinoic acid, triiodothyronine, and extracellular matrix. 919 74


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