New insights into TGF-β/Smad signaling in tissue fibrosis
New insights into TGF-β/Smad signaling in tissue fibrosis
复制标题
对组织纤维化中 TGF-β/Smad 信号传导的新见解
DOI：
10.1016/j.cbi.2018.07.008
复制
发表时间：
2018-08-25
影响因子：
5.1
通讯作者：
Zhao, Ying-Yong
中科院分区：
文献类型：
--
作者：
Hu, He-He;Chen, Dan-Qian;Zhao, Ying-Yong
转化生长因子-β 1（TGF-β 1）被认为是组织纤维化中的关键介质，并且主要通过激活其下游小母体对抗十肢麻痹（Smad）信号传导而引起组织瘢痕形成。不同的TGF-β信号在纤维化中发挥不同的作用。TGF-β 1直接激活Smad信号传导，其触发促纤维化基因过表达。大量研究表明，TGF-β 1/Smad通路的失调是组织纤维化的重要致病机制。Smad 2和Smad 3是促进TGF-β 1介导的组织纤维化的两个主要下游调节因子，而Smad 7作为TGF-β 1/Smad通路的负反馈调节因子，从而保护免受TGF-β 1介导的纤维化。本文综述了TGF-β/Smad信号通路在肾、肝、肺和心脏纤维化中的分子机制，并对其在体内外干预作用的分子机制进行了深入探讨。TGF-β/Smad信号通路在肿瘤或癌症中的作用也进行了讨论。此外，目前的进展还突出了靶向TGF-β/Smad信号通路用于预防组织纤维化。本文综述了组织纤维化的病理生理机制。提出了特定的挑战，并将其置于未来抗组织纤维化应用的背景下。
Transforming growth factor-beta 1 (TGF-beta 1) is considered as a crucial mediator in tissue fibrosis and causes tissue scarring largely by activating its downstream small mother against decapentaplegic (Smad) signaling. Different TGF-beta signalings play different roles in fibrogenesis. TGF-beta 1 directly activates Smad signaling which triggers pro-fibrotic gene overexpression. Excessive studies have demonstrated that dysregulation of TGF-beta 1/Smad pathway was an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulator that promote TGF-beta 1-mediated tissue fibrosis, while Smad7 serves as a negative feedback regulator of TGF-beta 1/Smad pathway thereby protects against TGF-beta 1-mediated fibrosis. This review presents an overview of the molecular mechanisms of TGF-beta/Smad signaling pathway in renal, hepatic, pulmonary and cardiac fibrosis, followed by an in-depth discussion of their molecular mechanisms of intervention effects both in vitro and in vivo. The role of TGF-beta/Smad signaling pathway in tumor or cancer is also discussed. Additionally, the current advances also highlight targeting TGF-beta/Smad signaling pathway for the prevention of tissue fibrosis. The review reveals comprehensive pathophysiological mechanisms of tissue fibrosis. Particular challenges are presented and placed within the context of future applications against tissue fibrosis.