New insights into TGF-β/Smad signaling in tissue fibrosis

被引：881

作者：

Hu, He-He ^{[1
]}

Chen, Dan-Qian ^{[1
]}

Wang, Yan-Ni ^{[1
]}

Feng, Ya-Long ^{[1
]}

Cao, Gang ^{[3
]}

Vaziri, Nosratola D. ^{[2
]}

Zhao, Ying-Yong ^{[1
]}

机构：

[1] Northwest Univ, Sch Life Sci, Minist Educ, Key Lab Resource Biol & Biotechnol Western China, 229 Taibai North Rd, Xian 710069, Shaanxi, Peoples R China

[2] Univ Calif Irvine, Sch Med, Div Nephrol & Hypertens, Irvine, CA 92897 USA

[3] Zhejiang Chinese Med Univ, Sch Pharm, 548 Binwen Rd, Hangzhou 310053, Zhejiang, Peoples R China

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2018年 / 292卷

基金：

中国国家自然科学基金;

关键词：

TGF-beta; Smad; Renal fibrosis; Pulmonary fibrosis; Cardiac fibrosis; Cancer; GROWTH-FACTOR-BETA; TO-MESENCHYMAL TRANSITION; ATTENUATES RENAL FIBROSIS; WNT/BETA-CATENIN PATHWAY; ANTI-DIURETIC ACTIVITIES; CHRONIC KIDNEY-DISEASE; SALVIANOLIC ACID-B; PORIA-COCOS; TRADITIONAL USES; TUBULOINTERSTITIAL FIBROSIS;

D O I：

10.1016/j.cbi.2018.07.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：76 / 83

页数：8

共 122 条

[1]

TGF-β requires the activation of canonical and non-canonical signalling pathways to induce skeletal muscle atrophy [J].