Cellular and molecular mechanisms of renal fibrosis.
Cellular and molecular mechanisms of renal fibrosis.
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DOI：
10.1038/nrneph.2011.149
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发表时间：
2011-10-18
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
肾纤维化，特别是肾小管间质纤维化，是几乎所有进行性慢性肾脏疾病的共同最终结果。肾纤维化也是预后的可靠预测因子和肾功能不全的主要决定因素。无论最初的原因如何，肾纤维化都是一个动态的聚合过程，由四个重叠阶段组成：启动、激活、执行和进展。持续损伤后未消退的炎症会进入纤维形成阶段（启动），并通过多种机制触发多种来源的基质生成细胞的激活和扩张，包括间质成纤维细胞和周细胞的激活、肾小管上皮细胞和内皮细胞的表型转变以及循环纤维细胞的募集。激活后，基质生成细胞会组装出一种多组分、整合素相关的蛋白质复合物，该复合物整合了来自各种纤维形成信号的输入，并协调基质组分的产生及其细胞外组装。多种细胞和分子事件，例如肾小管萎缩、微血管稀疏和组织缺氧，促进疤痕形成并确保恶性进展至终末期肾衰竭。这篇综述概述了我们目前对肾纤维化细胞和分子机制的理解，这可以为新治疗策略的开发提供新的见解。
Renal fibrosis, particularly tubulointerstitial fibrosis, is the common final outcome of almost all progressive chronic kidney diseases. Renal fibrosis is also a reliable predictor of prognosis and a major determinant of renal insufficiency. Irrespective of the initial causes, renal fibrogenesis is a dynamic and converging process that consists of four overlapping phases: priming, activation, execution and progression. Nonresolving inflammation after a sustained injury sets up the fibrogenic stage (priming) and triggers the activation and expansion of matrix-producing cells from multiple sources through diverse mechanisms, including activation of interstitial fibroblasts and pericytes, phenotypic conversion of tubular epithelial and endothelial cells and recruitment of circulating fibrocytes. Upon activation, matrix-producing cells assemble a multicomponent, integrin-associated protein complex that integrates input from various fibrogenic signals and orchestrates the production of matrix components and their extracellular assembly. Multiple cellular and molecular events, such as tubular atrophy, microvascular rarefaction and tissue hypoxia, promote scar formation and ensure a vicious progression to end-stage kidney failure. This Review outlines our current understanding of the cellular and molecular mechanisms of renal fibrosis, which could offer novel insights into the development of new therapeutic strategies.