Ma Yuan, Zou Hai, Zhu Xing-Xing, Pang Jie, Xu Qiang, Jin Qin-Yang, Ding Ya-Hui, Zhou Bing, Huang Dong-Sheng
Department of Cardiology, Zhejiang Provincial People's Hospital, Hangzhou, China.
People's Hospital of Hangzhou Medical College, Hangzhou, China.
Oncotarget. 2017 Apr 19;8(32):53780-53790. doi: 10.18632/oncotarget.17255. eCollection 2017 Aug 8.
Transforming growth factor β (TGF-β) is a multifunctional cytokine that is synthesized by many types of cells and regulates the cell cycle. Increasing evidence has led to TGF-β receiving increased and deserved attention in recent years because it may play a potentially novel and critical role in the development and progression of myocardial fibrosis and the subsequent progress of ventricular remodeling (VR). Numerous studies have highlighted a crucial role of TGF-β in VR and suggest potential therapeutic targets of the TGF-β signaling pathways for VR. Changes in TGF-β activity may elicit anti-VR activity and may serve as a novel therapeutic target for VR therapy. This review we discusses the smad-dependent signaling pathway, such as TGF-β/Smads, TGF-β/Sirtuins, TGF-β/BMP, TGF-β/miRNAs, TGF-β/MAPK, and Smad-independent signaling pathway of TGF-β, such as TGF-β/PI3K/Akt, TGF-β/Rho/ROCK,TGF-β/Wnt/β-catenin in the cardiac fibrosis and subsequent progression of VR. Furthermore, agonists and antagonists of TGF-β as potential therapeutic targets in VR are also described.
转化生长因子β（TGF-β）是一种多功能细胞因子，由多种类型的细胞合成并调节细胞周期。近年来，越来越多的证据表明TGF-β受到了越来越多且应有的关注，因为它可能在心肌纤维化的发生发展以及随后的心室重构（VR）进程中发挥潜在的新的关键作用。大量研究强调了TGF-β在VR中的关键作用，并提示了TGF-β信号通路作为VR潜在治疗靶点。TGF-β活性的改变可能引发抗VR活性，并可能成为VR治疗的新靶点。在本综述中，我们讨论了TGF-β的Smad依赖信号通路，如TGF-β/Smads、TGF-β/Sirtuins、TGF-β/BMP、TGF-β/miRNAs、TGF-β/MAPK，以及TGF-β的Smad非依赖信号通路，如TGF-β/PI3K/Akt、TGF-β/Rho/ROCK、TGF-β/Wnt/β-catenin在心脏纤维化及随后VR进程中的作用。此外，还描述了TGF-β激动剂和拮抗剂作为VR潜在治疗靶点。
