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成人肾脏的成熟小管上皮细胞在疾病状态下可发生上皮间充质转化,这种表型转化是肾间质纤维化的病理基础。越来越多的证据表明,病变肾脏大量的间质成纤维细胞实际上是由肾小管上皮细胞转化而来。上皮间充质转化由四步组成:(1)失去上皮粘附特性;(2)表达α-平滑肌肌动蛋白,肌动蛋白重排;(3)瓦解小管基底膜;(4)增强细胞移动性和侵袭性。很多生长因子、细胞因子、激素、细胞外信号调节上皮间充质转化过程,其中转化生长因子β1(TGF-β1)是最强的诱导因子,它在上皮间充质转化时发挥了重要作用。TGF-β1可单独引起并完成整个上皮间充质转化过程。肝细胞生长因子和骨形态形成蛋白-7是上皮间充质转化的抑制因子,能在体内和体外抑制上皮间充质转化的发生。多个细胞内信号转导通路介导了上皮间充质转化的发生,而Smad/整合素连接激酶可能起重要作用。该文综述了肾纤维化中上皮间充质转化的病理学意义、细胞分子机制、调节、信号转导通路和针对上皮间充质转化的治疗措施。
Mature tubular epithelial cells from adult kidneys may undergo epithelial mesenchymal transition under disease conditions. This phenotypic transformation is the pathological basis of renal interstitial fibrosis. There is growing evidence that a large number of interstitial fibroblasts in diseased kidneys are actually transformed by renal tubular epithelial cells. Epithelial mesenchymal transition is composed of four steps: (1) loss of epithelial adhesion properties; (2) expression of α-smooth muscle actin, actin rearrangement; (3) disruption of the tubulointerstitial membrane; (4) Sexual and aggressive. Many growth factors, cytokines, hormones and extracellular signals regulate the process of epithelial mesenchymal transition. Among them, transforming growth factor β1 (TGF-β1) is the strongest inducing factor and plays an important role in epithelial mesenchymal transition. TGF-β1 alone can lead to and complete the entire process of epithelial mesenchymal transition. Hepatocyte growth factor and bone morphogenetic protein-7, as inhibitors of epithelial mesenchymal transition, inhibit epithelial mesenchymal transition both in vitro and in vivo. Multiple intracellular signal transduction pathways mediate epithelial mesenchymal transition, and Smad / integrin ligation kinase may play an important role. This review summarizes the pathological significance of epithelial mesenchymal transition in renal fibrosis, the cellular molecular mechanisms, regulation, signal transduction pathways, and therapies that target epithelial mesenchymal transition.