TGF-β1 inhibits apoptosis of cardiomyocytes H9c2 by regulating autophagy and ERK pathway.

Abstract

This study aimed to explore the expression and mechanism of transforming growth factor β1 (TGF-β1) in oxygen glucose deprivation reperfusion (OGD/R)-induced ischemia/reperfusion (I/R) injury. An OGD/R model was established in cardiomyocytes H9c2, resulting in upregulation of Beclin-1 and LC3II/LC3I expression. Upon overexpression of TGF-β1, the viability of OGD/R-induced H9c2 cells was enhanced, while apoptosis was suppressed by downregulating Bax and upregulating Bcl-2. Additionally, TGF-β1 overexpression promoted autophagy in OGD/R-induced H9c2 cells by further upregulating the levels of Beclin-1 and LC3II/LC3I. Importantly, treatments with 3-methyladenine (3-MA), an autophagy inhibitor, and U0126, an extracellular signal-related kinases 1 and 2 (ERK1/2) inhibitor, significantly inhibited cell viability, increased intracellular reactive oxygen species levels, promoted cell apoptosis (by upregulating Bax and downregulating Bcl-2), and inhibited cell autophagy (by downregulating Beclin-1 and LC3II/LC3I) in OGD/R-induced H9c2 cells with TGF-β1 overexpression. Additionally, OGD/R induction significantly increased the levels of p-ERK, p-P38, and p-JNK, which were further enhanced by TGF-β1 overexpression. U0126 treatments significantly downregulated the p-ERK compared to OGD/R-induced H9c2 cells with TGF-β1 overexpression. Our study suggests that TGF-β1 could inhibit the growth of cardiomyocytes H9c2 by regulating autophagy and ERK pathways, providing a new theoretical basis for the treatment and prevention of OGD/R in clinical practice.