TRANSFORMING GROWTH-FACTOR BETA-MODULATES THE EXPRESSION OF COLLAGENASE AND METALLOPROTEINASE INHIBITOR
TRANSFORMING GROWTH-FACTOR BETA-MODULATES THE EXPRESSION OF COLLAGENASE AND METALLOPROTEINASE INHIBITOR
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DOI：
10.1002/j.1460-2075.1987.tb02449.x
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发表时间：
1987-07-01
期刊：
影响因子：
11.4
通讯作者：
HEATH, JK
中科院分区：
文献类型：
--
作者：
EDWARDS, DR;MURPHY, G;HEATH, JK
静止MRC-5人成纤维细胞暴露于生长因子，如表皮生长因子，碱性成纤维细胞生长因子或胚胎癌源性生长因子导致诱导的mRNA转录编码的金属蛋白酶胶原酶和基质溶解素和特异性金属蛋白酶抑制剂TIMP，而胶原蛋白和纤连蛋白的表达相对不受影响。在存在转化生长因子β（TGF-β）的情况下将静止细胞暴露于生长因子导致胶原酶诱导的抑制和TIMP表达的协同增加。TGF-.beta.单独没有显著诱导金属蛋白酶或TIMP表达。这些对mRNA转录的影响反映在TIMP蛋白和胶原酶活性的分泌增加。生长因子诱导的转录的核流出分析揭示TGF-βTIMP和胶原酶表达的调节是由于转录机制。观察结果表明，TGF-β.通过调节其他生长因子对金属蛋白酶和TIMP表达的作用，对细胞外基质沉积发挥选择性作用。
Exposure of quiescent MRC-5 human fibroblasts to growth factors such as epidermal growth factor, basic fibroblast growth factor or embryonal carcinoma-derived growth factor resulted in the induction of mRNA transcripts encoding the metalloproteinases collagenase and stromelysin and the specific metalloproteinase inhibitor TIMP, while expression of collagen and fibronectin was relatively unaffected. Exposure of quiescent cells to growth factors in the presence of transforming growth factor beta (TGF-.beta.) resulted in inhibition of collagenase induction and a synergistic increase in TIMP expression. TGF-.beta. alone did not significantly induce metalloproteinase or TIMP expression. These effects on mRNA transcripts were reflected in increased secretion of TIMP protein and collagenase activity. Nuclear run-off analysis of growth factor-induced transcription revealed that the TGF-.beta. modulation of TIMP and collagenase expression was due to transcriptional mechanisms. The observations suggest that TGF-.beta. exerts a selective effect on extracellular matrix deposition by modulating the action of other growth factors on metalloproteinase and TIMP expression.