Wnt/β-catenin signaling and kidney fibrosis.
Wnt/β-catenin signaling and kidney fibrosis.
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DOI：
10.1038/kisup.2014.16
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发表时间：
2014-11
影响因子：
5.5
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Tan RJ;Zhou D;Zhou L;Liu Y
Wnt/β-catenin信号传导是一种进化上保守的、高度复杂的关键发育途径，其调节细胞命运、器官发育、组织稳态以及损伤和修复。尽管在正常成人肾脏中相对沉默，但在多种动物模型和人类肾脏疾病中，Wnt/β-连环蛋白信号传导在肾损伤后重新激活。尽管一些数据指出这种信号传导在急性肾损伤后的愈合和修复中具有保护作用，但越来越多的证据表明Wnt/β-连环蛋白的持续活化与肾纤维化病变的发展和进展相关。在肾细胞中，Wnt/β-catenin促进许多纤维化相关基因的表达，如Snail 1、纤溶酶原激活物抑制剂-1和基质金属蛋白酶-7。最近的研究还表明，肾素-血管紧张素系统的多个组分是Wnt/β-catenin的直接下游靶点。一致地，通过各种策略抑制Wnt/β-连环蛋白信号传导改善了各种慢性肾病模型中的肾损伤并减轻了肾纤维化病变，表明靶向该信号传导可能是治疗干预的合理策略。本文就Wnt/β-catenin信号通路在肾纤维化发病机制中的调控、下游靶点及作用机制作一简要综述。
Wnt/β-catenin signaling is an evolutionarily conserved, highly complex, key developmental pathway that regulates cell fate, organ development, tissue homeostasis, as well as injury and repair. Although relatively silent in normal adult kidney, Wnt/β-catenin signaling is re-activated after renal injury in a wide variety of animal models and in human kidney disorders. Whereas some data point to a protective role of this signaling in healing and repair after acute kidney injury, increasing evidence suggests that sustained activation of Wnt/β-catenin is associated with the development and progression of renal fibrotic lesions. In kidney cells, Wnt/β-catenin promotes the expression of numerous fibrosis-related genes such as Snail1, plasminogen activator inhibitor-1, and matrix metalloproteinase-7. Recent studies also indicate that multiple components of the renin–angiotensin system are the direct downstream targets of Wnt/β-catenin. Consistently, inhibition of Wnt/β-catenin signaling by an assortment of strategies ameliorates kidney injury and mitigates renal fibrotic lesions in various models of chronic kidney disease, suggesting that targeting this signaling could be a plausible strategy for therapeutic intervention. In this mini review, we will briefly discuss the regulation, downstream targets, and mechanisms of Wnt/β-catenin signaling in the pathogenesis of kidney fibrosis.