TGFBR3, a potential negative regulator of TGF‐β signaling, protects cardiac fibroblasts from hypoxia‐induced apoptosis

Abstract

A lot of evidence indicates that cardiac fibroblasts are essential for maintaining the structure and function of heart. The present study examined whether TGFBR3 (transforming growth factor type III receptor, also known as betaglycan) could prevent hypoxia-induced injury in neonatal mice cardiac fibroblasts, if so, its possible molecular targets. MTT, electron microscopy and TUNEL assay were used to identify cell viability and apoptosis in neonatal mice cardiac fibroblasts. Results showed that hypoxia for 24 h markedly reduce cell viability by 49.8 ± 8.9%, largely via apoptosis. However, hypoxia-induced apoptosis in cardiac fibroblasts were almost completely prevented by overexpression of TGFBR3. In the present study, hypoxia also induced TGF-β1, p-Smad2/3 expression, TGFBR1-TGFBR2 complex formation and collagen production in cardiac fibroblasts, which were attenuated substantially by TGFBR3 overexpression. TGFBR3 also reversed Bax up-regulation, Bcl-2 down-regulation and Caspase-3 activation induced by hypoxia in cardiac fibroblasts. Hypoxia or TGF-β1 itself triggered an increase of [Ca(2+) ](i) in cardiac fibroblasts, which were both inhibited by TGFBR3 overexpression. Taken together, our results indicate that TGFBR3 may act as a protective factor in apoptotic process of cardiac fibroblasts by negative regulation of TGF-β signaling and represent a potential therapeutic target for heart remodeling after hypoxia injury.

Transforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis

“…Under H 2 O 2 conditions, an increase in TGFβR3 levels exerts a cumulative effect on the degree of apoptosis. Consistently, TGFβR3 is also known to enhance apoptosis in some tumor cells; however, TGFβR3 suppresses the apoptosis of cardiofibroblasts,7, 10 potentially by deactivating the TGFβR1/TGFβR2 complex to downregulate cell apoptosis 24. According to our data, TGFβR3 promotes cardiomyocyte apoptosis induced by myocardial infarction.…”

Identification of Docetaxel Resistance Genes in Castration-Resistant Prostate Cancer

“…As a member of this family, TGFBR3 acts as a coreceptor of TGF-b ligand, being a positive or negative regulator of TGF-b signals depending on the cellular context (42; 43). Recently, it has been shown that TGFBR3 may act as a protective factor in the apoptotic process of fibroblasts by negative regulation of TGF-b signaling (44). Our results further suggest that TGFB1 acts as a protective factor against docetaxel for DU-145 and PC-3 cells and has a partial role in the development of docetaxel resistance in cultured cells.…”

Transforming Growth Factor Beta in the Central Nervous System

“…However, it is an extracellular protein, which does not lead to signal transduction. In fact, it may be a negative regulator of TGF-β function (Chu et al, 2011).…”