Transforming growth factor β: A potential biomarker and therapeutic target of ventricular remodeling

// Yuan Ma 1, 5, * , Hai Zou 1, 5, * , Xing-Xing Zhu 2, 5, * , Jie Pang 1, 5 , Qiang Xu 1, 5 , Qin-Yang Jin 1, 5 , Ya-Hui Ding 1, 5 , Bing Zhou 3, 5 and Dong-Sheng Huang 4, 5 1 Department of Cardiology, Zhejiang Provincial People's Hospital, Hangzhou, China 2 Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, China 3 Department of Cardiac Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China 4 Department of Hepatobiliary Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China 5 People’s Hospital of Hangzhou Medical College, Hangzhou, China * Co-first authors Correspondence to: Bing Zhou, email: zhoubing@zjheart.com Ya-Hui Ding, email: dyh@zjheart.com Hai Zou, email: haire1993@163.com Dong-Sheng Huang, email: dshuang@zjheart.com Keywords: transforming growth factor β, myocardial fibrosis, ventricular remodeling, mechanism, targets Received: February 06, 2017      Accepted: April 11, 2017      Published: April 19, 2017 ABSTRACT 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.