TGF-β signaling via TAK1 pathway: role in kidney fibrosis.

TGF-β signaling via TAK1 pathway: role in kidney fibrosis.
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DOI:
10.1016/j.semnephrol.2012.04.003
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发表时间:
2012-05
影响因子:
3.3
通讯作者:
Kim, Sung Il
Kim, Sung Il
中科院分区:
医学2区
文献类型:
--
作者:
Choi, Mary E.;Ding, Yan;Kim, Sung Il

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在进展性肾脏疾病中,纤维化是终末期肾功能衰竭的常见途径。转化生长因子-β-1(Transform Growth Factor-β-1,TGF1)是一种多效性细胞因子,已被认为是肾纤维化的中枢介质。新出现的证据表明,一个复杂的信号网络方案,使多功能的转化生长因子-β1的作用。特异性靶向转化生长因子-β信号通路似乎是一种关键和有吸引力的分子治疗策略。转化生长因子-β1信号通过I型(TβRI)和II型(TβRII)受体的相互作用激活涉及Smad和非Smad的不同的细胞内通路。Smad信号轴被认为是转化生长因子-β-1诱导的典型信号通路。重要的是,最近的研究表明,转化生长因子-β-1还可以诱导多种非Smad信号通路。本文就Smad非依赖性信号转导通路的机制、功能及其在转化生长因子-β-激活蛋白1促纤维化作用中的作用作一综述。
In progressive kidney diseases, fibrosis represents the common pathway to end-stage kidney failure. Transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine that has been established as a central mediator of kidney fibrosis. Emerging evidence demonstrates a complex scheme of signaling networks that enable multifunctionality of TGF-β1 actions. Specific targeting of TGF-β signaling pathway is seemingly critical and attractive molecular therapeutic strategy. TGF-β1 signals through the interaction of type I (TβRI) and type II (TβRII) receptors to activate distinct intracellular pathways involving the Smad and the non-Smad. The Smad signaling axis is known as the canonical pathway induced by TGF-β1. Importantly, recent investigations show that TGF-β1 also induces various non-Smad signaling pathways. In this review, we focus on current insights into the mechanism and function of Smad-independent signaling pathway via TGF-β-activated kinase 1 (TAK1) and its role in mediating the profibrotic effects of TGF-β1.
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