The effect of mechanical stretch on TGF-beta and extracellular matrix expression in glomerular cells.

我们研究了机械牵张对培养的肾小球系膜细胞中各种生长因子和细胞外基质（ECM）成分表达的影响。机械拉伸刺激TGF-β 1和TGF-β 3的mRNA表达的时间和延长依赖性的方式，和细胞分泌大量的TGF-β蛋白几乎作为一个潜在的形式，这是增加响应拉伸。牵张还刺激了I型和IV型胶原以及系膜ECM的主要成分纤连蛋白的mRNA表达。牵张诱导的ECM表达主要由牵张诱导的TGF-β的自分泌/旁分泌介导。机械拉伸也刺激了所有TGF-β R亚型（I型、II型和III型受体）的mRNA表达，并且<125>拉伸实际上增加了I标记的TGF-β与每个TGF-β R亚型的结合。机械牵张还刺激PDGF A链和B链的mRNA表达。拉伸诱导的TGF-β mRNA表达被酪氨酸激酶抑制剂抑制。此外，牵张诱导的ECM和TGF-β表达均被抗PDGF中和抗体部分抑制。这些结果表明，机械拉伸上调TGF-β受体，并通过酪氨酸激酶依赖性机制增加TGF-β的表达/分泌，这是由stetch诱导的PDGF增强，导致在培养的系膜细胞拉伸后高水平的ECM表达。结果表明，TGF-β和PDGF可能在体内肾小球高血压引起的肾小球硬化的进展中起重要作用。

We examined the effect of mechanical stretch on the expression of various growth factors and extracellular matrix(ECM)components in cultured glomerular mesangial cells. Mechanical stretch stimulated mRNA expression of TGF-beta1 and TGF-beta3 in a time- and elongation-dependent manner, and the cells secreted substantial amounts of TGF-beta proteins almost as a latent form, which was increased in response to stretch. Stretch also stimulated mRNA expression of collagen types I and IV,and fibronectin, major components of mesangial ECM.The stretch-induced ECM expression was largely mediated by autocrine/paracrine secretion of TGF-beta induced by stretch. Mechanical stretch also stimulated mRNA expression of all TGF-betaR isoforms, type I,II and III receptors and the binding of ^<125>I-labeled TGF-beta to each TGF-betaR isoform was actually increased by stretch. Mechanical stretch also stimulated mRNA expression of PDGF A- and B-chain. The stretch-induced mRNA expression of TGF-beta was inhibited by tyrosine kinase inhibitors. Moreover, the stretchinduced ECM and TGF-beta expression was both partially inhibited by anti-PDGF neutralizing antibody. These results show that mechanical stretch upregulates TGF-beta receptors and increases TGF-beta expression/secretion through tyrosine kinase-dependent mechanisms, which is enhanced by the stetch-induced PDGF,resulting in high levels of ECM expression after stretch in cultured mesangial cells. The results suggest that TGF-beta and PDGF may play an important role in the progression of glomerulosclerosis by glomerular hypertension in vivo.