New insights into epithelial-mesenchymal transition in kidney fibrosis.
New insights into epithelial-mesenchymal transition in kidney fibrosis.
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DOI：
10.1681/asn.2008121226
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Liu Y
中科院分区：
文献类型：
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作者：
Liu Y
上皮-间充质转化（epithelial -mesenchymal transition， EMT）是一个分化的上皮细胞经过表型转化，产生基质生成的成纤维细胞和肌成纤维细胞的过程，越来越被认为是损伤后组织纤维形成的一个组成部分。然而，这一过程在多大程度上导致肾纤维化仍然是一个激烈争论的问题，并且可能与环境有关。EMT通常发生在慢性间质炎症之前，并与慢性间质炎症密切相关，可能是上皮细胞对敌对或变化的微环境的适应性反应。最近的研究表明，除了小管上皮细胞外，内皮细胞和肾小球足细胞也可能在损伤后发生转变。足细胞的表型改变使其运动功能受损，导致蛋白尿和肾小球硬化。一些细胞内信号转导通路，如TGFβ/Smad，整合素连接激酶（ILK）和Wnt/β-catenin信号通路在控制EMT过程中是必不可少的，目前是抗纤维化治疗的潜在靶点。这篇综述强调了目前对EMT及其潜在机制的理解，以激发对其作用的进一步讨论，不仅在肾间质纤维化的发病机制中，而且在足细胞功能障碍、蛋白尿和肾小球硬化的发病中。
Epithelial-mesenchymal transition (EMT), a process by which differentiated epithelial cells undergo a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury. However, the degree to which this process contributes to kidney fibrosis remains a matter of intense debate and is likely to be context-dependent. EMT is often preceded by and closely associated with chronic interstitial inflammation and could be an adaptive response of epithelial cells to a hostile or changing microenvironment. In addition to tubular epithelial cells, recent studies indicate that endothelial cells and glomerular podocytes may also undergo transition after injury. Phenotypic alteration of podocytes sets them in motion to functional impairment, resulting in proteinuria and glomerulosclerosis. Several intracellular signal transduction pathways such as TGFβ/Smad, integrin-linked kinase (ILK) and Wnt/β-catenin signaling are essential in controlling the process of EMT and presently are potential targets of antifibrotic therapy. This review highlights the current understanding of EMT and its underlying mechanisms to stimulate further discussion on its role, not only in the pathogenesis of renal interstitial fibrosis but also in the onset of podocyte dysfunction, proteinuria, and glomerulosclerosis.