Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Semin Nephrol. 2012 May;32(3):244-52. doi: 10.1016/j.semnephrol.2012.04.003.
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 shows a complex scheme of signaling networks that enable multifunctionality of TGF-β1 actions. Specific targeting of the TGF-β signaling pathway is seemingly critical and an attractive molecular therapeutic strategy. TGF-β1 signals through the interaction of type I and type II 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 have shown that TGF-β1 also induces various non-Smad signaling pathways. In this review, we focus on current insights into the mechanism and function of the Smad-independent signaling pathway via TGF-β-activated kinase 1 and its role in mediating the profibrotic effects of TGF-β1.
在进行性肾脏疾病中，纤维化是导致终末期肾衰竭的共同途径。转化生长因子-β1（TGF-β1）是一种多功能细胞因子，已被确立为肾脏纤维化的主要介质。新出现的证据显示了一个复杂的信号网络方案，使 TGF-β1 发挥多种功能。针对 TGF-β 信号通路的特异性靶向似乎是关键的，也是一种有吸引力的分子治疗策略。TGF-β1 通过 I 型和 II 型受体的相互作用信号转导，激活涉及 Smad 和非 Smad 的不同细胞内途径。Smad 信号轴被称为 TGF-β1 诱导的经典途径。重要的是，最近的研究表明，TGF-β1 还诱导各种非 Smad 信号通路。在这篇综述中，我们重点介绍了通过 TGF-β 激活激酶 1 介导的 Smad 非依赖性信号通路的机制和功能的最新见解，以及其在介导 TGF-β1 致纤维化作用中的作用。
