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.
Highlights
Ventricular remodeling (VR) is a complicated process involving cardiomyocyte hypertrophy, inflammation, fibrosis and occurs in response to changes in mechanical and neurohormonal stimulation [1]
Did Transforming growth factor β (TGF-β)/Smads play a dual role in the regulation of TGF-β, but sirtuins played an important role in regulating TGF-β
Sirt1 had the ability to negatively regulate the expression of Smad7 and decrease the inhibition of TGF-β/Smad7, thereby decreasing fibrosis
Summary
Ventricular remodeling (VR) is a complicated process involving cardiomyocyte hypertrophy, inflammation, fibrosis and occurs in response to changes in mechanical and neurohormonal stimulation [1]. Another study showed shown that angiotensin II (AngII) induced left ventricular fibrosis and remodeling, which were dependent on both Smad2 and extracellular regulated protein kinase (ERK) activation, and could be inhibited by the AT1 receptor [7]. In an analysis of AngII-induced VR, Wei et al found that Smad7 attenuated cardiac inflammation and fibrosis, such as by down-regulating IL-1β and TNF-α, inhibited collagen I and α-SMA and suppressed Ang IImediated VR [16].
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