Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of transforming growth factor-beta 1 (TGF-beta 1) on matrix gene expression has been investigated during the process of wound repair, where the formation of new connective tissue represents a critical step in restoring tissue integrity. Split-thickness excisional wounds in the pig were studied by in situ hybridization in order to obtain subjective findings on the activity and location of cells involved in matrix gene expression after the administration of recombinant TGF-beta 1. Data focus on the stimulatory role of this growth factor in granulation tissue formation, on the enhanced mRNA content of collagen types I and III, fibronectin, TGF-beta 1 itself, and on the reduction in stromelysin mRNA, suggesting that increased matrix formation measured after treatment with TGF-beta 1 is due to fibroplasia regulated by the abundance of mRNAs for several different structural, matrix proteins as well as inhibition of proteolytic phenomena elicited by metalloproteinases. These studies reveal elastin mRNA early in the repair process, and elastin mRNA expression is enhanced by administration of TGF-beta 1. Moreover, we show that TGF-beta 1 was auto-stimulating in wounds, accounting, at least in part, for the persistent effects of single doses of this multipotential cytokine.
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PMID:Transforming growth factor-beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin. I. Excisional wound model. 239 27

The gene expressions of type I collagen and transforming growth factor-beta 1 (TGF-beta 1) were studied in lung tissue of rats exposed to air or 85% O2 for 14 days. Peak expression of type I collagen mRNA was observed by 14 days of 85% O2 exposure, at the same time as maximal immunoreactive type I collagen, which was most marked surrounding the major airways and vessels. TGF-beta 1 mRNA also significantly increased after 14, but not 4 or 6 days of 85% O2 exposure. TGF-beta 1 immunoreactivity was only detected on day 14 of 85% O2 exposure and was localized primarily to the pulmonary epithelium. As an increase in immunoreactive type I collagen was evident by day 6 of O2 exposure, the gene expressions of interstitial collagenase (MMP-1), stromelysin, and the tissue inhibitor of the metalloproteinases (TIMP) were also examined. Increased mRNA expressions of interstitial collagenase and TIMP preceded those of type I collagen and TGF-beta 1, occurring at 4-6 days of exposure to 85% O2, while there was no significant change in stromelysin mRNA. These findings are compatible with the initial O2-mediated increase in type I collagen deposition being a result of an altered proteinase/antiproteinase balance in the lung, and the subsequent more marked deposition being a response to increased TGF-beta 1 synthesis.
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PMID:Altered expression of type I collagen, TGF-beta 1, and related genes in rat lung exposed to 85% O2. 784 Feb 32

Nephrotic syndrome induced by puromycin aminonucleoside (PAN) is characterized by tubulointerstitial (TI) inflammation, foci of TI fibrosis, and increased renal mRNA levels for matrix genes, the tissue inhibitor of metalloproteinases (TIMP), and the transforming growth factor-beta 1 (TGF-beta 1). To investigate the ability of a low-protein diet known to decrease TI inflammation to alter the degree of renal fibrosis, we studied four groups of rats: 27% protein PAN, 27% protein control, 8% protein PAN, and 8% protein control. Renal TGF-beta 1 mRNA levels correlated with the number of interstitial macrophages (r = 0.76) and were significantly reduced by dietary protein restriction. On day 10, Northern blot analysis showed that the elevated renal mRNA levels for procollagens alpha 1 (I), alpha 1(III), and alpha 2(IV) and fibronectin in the PAN-treated rats were significantly reduced by 8% dietary protein. In contrast, genes regulating matrix degradation (stromelysin and TIMP) were relatively unchanged by the low-protein diet. The number of foci of interstitial fibrosis and total renal collagen were greater in the PAN + 27% protein group than in the control groups. Both parameters of fibrosis were partially normalized in the PAN + 8% protein group. The results of this study suggest that dietary protein restriction attenuates TI fibrosis in PAN-induced nephrosis by partially reversing the increase in renal matrix synthesis. This effect was associated with decreased renal expression of the fibrogenic cytokine TGF-beta 1, which may be partially mediated by the concomitant reduction in the number of interstitial inflammatory macrophages.
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PMID:Protein restriction reduces transforming growth factor-beta and interstitial fibrosis in nephrotic syndrome. 802 68

1. Pig synovial fibroblasts in culture were studied to determine if they were an easily reproducible model system for studying the actions of cytokines and growth factors on human synovial cells. The biochemical analyses were conducted by activity assays, enzymography and Northern blot. 2. Human recombinant interleukin-1 alpha, basic fibroblast growth factor and transforming growth factor-beta 1 were studied in combinations because of their known involvement in controlling tissue remodelling. 3. The response of pig fibroblasts to these agents, in terms of the expression of matrix metalloproteinases (collagenase, gelatinase and stromelysin) and their inhibitors (TIMPs), show that they behave similarly enough to human cells for use when supplies of human primary cells are unavailable.
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PMID:The expression of matrix metalloproteinases and their inhibitors by pig synovial cells and their regulation by combinations of cytokines and growth factors. 828 64

Production of matrilysin and stromelysin by five human glioma cell lines was investigated by Northern blot and immunoblot analyses. Four cell lines constitutively produced matrilysin. Its production was stimulated by phorbol-12-myristate-13-acetate (PMA) in two cell lines and by transforming growth factor-beta 1 (TGF-beta 1) in two other cell lines. Stromelysin transcript was constitutively expressed in only two cell lines, but enhanced or induced by PMA in four cell lines. These results suggest that these enzymes, especially matrilysin, may be involved in the invasive growth of neoplastic glial cells.
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PMID:Expressions of matrilysin and stromelysin in human glioma cells. 850 12

The balance between the activities of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) is an important control point in tissue remodeling. Previous studies have demonstrated elevated expression of the MMPs collagenase and stromelysin-1 by aged human diploid fibroblasts compared to early-passage cultures. We show here that aging cells display an altered response to transforming growth factor-beta 1 (TGF beta 1) that selectively affects MMP mRNA expression. In both young and old cells, phorbol myristoyl-13 acetate (PMA) induced the expression of transcripts of collagenase, stromelysin-1, gelatinase-B, TIMP-1, and TIMP-3. In young cells, TGF beta 1 reciprocally modulated PMA-induced MMP and TIMP gene expression leading to reduced levels of transcripts for the MMPs and augmented accumulation of TIMP-1 and TIMP-3 mRNAs. However, repressing effects of TGF beta 1 on collagenase, stromelysin-1, and gelatinase-B RNA expression were not apparent in old cells, though induction of the TIMP genes was unimpaired. By electrophoretic mobility shift analysis the nuclear transcription factors AP1 and serum response factor (SRF) showed reduced levels of DNA binding activities in old fibroblasts compared to young cells. A probe for the TGF beta-inhibitory element (TIE) gave equivalent levels of complexes with nuclear extracts from both types of cells, though of different mobilities. We conclude that the effects of TGF beta 1 on MMP and TIMP gene expression involve different cellular intermediaries, and suggest that altered composition or modification of TIE binding factors in aging cells may underlie the failure of TGF beta 1-mediated transcription repression. This mechanism may contribute to elevated constitutive expression of MMPs in old cells and to the connective tissue deterioration that accompanies the aging process.
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PMID:Differential effects of transforming growth factor-beta 1 on the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in young and old human fibroblasts. 870 90