TGF-β1-Induced Epithelial-to-Mesenchymal Transition and Therapeutic Intervention in Diabetic Nephropathy
TGF-β1-Induced Epithelial-to-Mesenchymal Transition and Therapeutic Intervention in Diabetic Nephropathy
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DOI：
10.1159/000256659
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Squires, Paul E.
中科院分区：
文献类型：
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作者：
Hills, Claire E.;Squires, Paul E.
背景/目的：上皮间质细胞转化（EMT）是肾小管上皮细胞向肌成纤维细胞的转分化，这是糖尿病进行性慢性肾病的潜在事件，导致纤维化。 EMT 主要发生在肾脏近端区域，现在被认为是糖尿病肾病 (DN) 整个肾单位肾功能丧失的关键因素。糖尿病中 TGF-β 的同时上调使得这种促纤维化细胞因子成为这些纤维化并发症发展的明显候选者。本文回顾了最近的研究结果，阐明了我们对 TGF-β 和相关亚细胞蛋白在 EMT 中的作用的理解。方法：为了了解 EMT 的病理学和 TGF-β 的作用，我们使用 PubMed 查阅了包含 EMT、TGF-β 和 DN 相关关键词的英文文章。结果：整个肾单位上皮细胞的 EMT 和表型可塑性涉及细胞骨架重组和经典间充质标志物的从头获得。上皮粘附分子的同时下调会导致功能丧失和细胞耦合减少，从而导致上皮完整性丧失。 TGF-β1 在介导这些表型变化中发挥着关键作用。结论：TGF-β 诱导的 EMT 是 DN 中纤维化疤痕形成的关键因素，并讨论了未来治疗干预的新途径。版权所有 (c) 2009 S. Karger AG，巴塞尔
Background/Aims: Epithelial-to-mesenchymal cell transformation (EMT) is the trans-differentiation of tubular epithelial cells into myofibroblasts, an event underlying progressive chronic kidney disease in diabetes, resulting in fibrosis. Mainly reported in proximal regions of the kidney, EMT is now recognized as a key contributor to the loss of renal function throughout the nephron in diabetic nephropathy (DN). Concomitant upregulation of TGF-beta in diabetes makes this pro-fibrotic cytokine an obvious candidate in the development of these fibrotic complications. This article reviews recent findings clarifying our understanding of the role of TGF-beta and associated sub-cellular proteins in EMT. Methods: To understand the pathology of EMT and the role of TGF-beta, we reviewed the literature using PubMed for English language articles that contained key words related to EMT, TGF-beta and DN. Results: EMT and phenotypic plasticity of epithelial cells throughout the nephron involves cytoskeletal reorganization and de novo acquisition of classic mesenchymal markers. Concurrent downregulation of epithelial adhesion molecules results in a loss of function and decreased cell coupling, contributing to a loss of epithelial integrity. TGF-beta 1 is pivotal in mediating these phenotypic changes. Conclusion: TGF-beta-induced EMT is a key contributor to fibrotic scar formation as seen in DN, and novel routes for future therapeutic intervention are discussed. Copyright (c) 2009 S. Karger AG, Basel