Raghow R, Postlethwaite A E, Keski-Oja J, Moses H L, Kang A H
J Clin Invest. 1987 Apr;79(4):1285-8. doi: 10.1172/JCI112950.
Transforming growth factor-beta (TGF beta), when injected subcutaneously into newborn mice, induces a rapid fibrotic response, stimulates chemotaxis, and elevates the rates of biosynthesis of collagen and fibronectin by fibroblasts in vitro. We explored the molecular mechanisms of TGF beta-mediated stimulation of collagen and fibronectin synthesis in cultured human foreskin fibroblasts. TGF beta preferentially stimulated the synthesis of fibronectin and type I procollagen chains 3-5-fold as shown by polypeptide analysis. Concomitant elevation in the steady state levels of messenger RNAs (mRNAs) coding for type I procollagen and fibronectin also occurred but without a net increase in the rate of transcription of either of these genes. The preferential stabilization of mRNAs specifying type I procollagen and fibronectin provides a partial explanation for the mechanisms by which TGF beta enhances the synthesis of type I procollagen and fibronectin in mesenchymal cells.
转化生长因子-β(TGF-β)皮下注射到新生小鼠体内时,会引发快速的纤维化反应,刺激趋化性,并在体外提高成纤维细胞中胶原蛋白和纤连蛋白的生物合成速率。我们探究了TGF-β介导的培养人包皮成纤维细胞中胶原蛋白和纤连蛋白合成刺激的分子机制。如多肽分析所示,TGF-β优先刺激纤连蛋白和I型前胶原链的合成达3至5倍。编码I型前胶原和纤连蛋白的信使核糖核酸(mRNA)的稳态水平也随之升高,但这两个基因的转录速率均未出现净增加。指定I型前胶原和纤连蛋白的mRNA的优先稳定作用为TGF-β增强间充质细胞中I型前胶原和纤连蛋白合成的机制提供了部分解释。