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

• Published in: Chemico-biological interactions Vol. 292; pp. 76 - 83
• Main Authors: Hu, He-He, Chen, Dan-Qian, Wang, Yan-Ni, Feng, Ya-Long, Cao, Gang, Vaziri, Nosratola D., Zhao, Ying-Yong
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 25.08.2018
• Subjects: Cancer; Cardiac fibrosis; Pulmonary fibrosis; Renal fibrosis; Smad; TGF-β; Cardiac fibrosis; TGF-β; Smad; Pulmonary fibrosis; Renal fibrosis; Cancer
• ISSN: 0009-2797; 1872-7786; 1872-7786
• DOI: 10.1016/j.cbi.2018.07.008

Transforming growth factor-β1 (TGF-β1) 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-β signalings play different roles in fibrogenesis. TGF-β1 directly activates Smad signaling which triggers pro-fibrotic gene overexpression. Excessive studies have demonstrated that dysregulation of TGF-β1/Smad pathway was an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulator that promote TGF-β1-mediated tissue fibrosis, while Smad7 serves as a negative feedback regulator of TGF-β1/Smad pathway thereby protects against TGF-β1-mediated fibrosis. This review presents an overview of the molecular mechanisms of TGF-β/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-β/Smad signaling pathway in tumor or cancer is also discussed. Additionally, the current advances also highlight targeting TGF-β/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. •TGF-β1 is considered as a crucial mediator in tissue fibrosis.•TGF-β1/Smad pathway is an important pathogenic mechanism in tissue fibrosis.•TGF-β/Smad pathway in cardiac, hepatic, pulmonary and renal fibrosis are discussed.•Targeting TGF-β/Smad pathway is an important therapeutic strategy for fibrosis.