Inhibitory effects of oxymatrine on TGF‑β1‑induced proliferation and abnormal differentiation in rat cardiac fibroblasts via the p38MAPK and ERK1/2 signaling pathways.

Interstitial fibrosis serves a causal role in the development of heart failure following acute and chronic myocardial infarction, and anti‑fibrotic therapy represents a promising strategy to mitigate this pathological process. Oxymatrine (OMT) exerts a number of pharmacological effects on the cardiovascular system, but its anti‑cardiovascular disease mechanisms remain unclear. The purpose of the present study was to investigate the effect of OMT administration on transforming growth factor (TGF)‑β1‑induced cardiac fibroblast (CFB) proliferation and abnormal differentiation, and to elucidate the underlying mechanisms. Primary CFBs were isolated from neonatal rats and used for experimental treatments. TGF‑β1 stimulation in CFBs resulted in increased proliferation, increased α‑smooth muscle actin (SMA) and type I and type III collagen expression, and increased p38 mitogen‑activated protein kinase (MAPK) and extracellular signal‑regulated kinase (ERK)1/2 phosphorylation. Treatment with OMT and SB431542 (a TGF‑β1 receptor inhibitor) attenuated the proliferation and abnormal differentiation of CFBs induced by TGF‑β1, and decreased p38MAPK and ERK1/2 phosphorylation. In addition, treatment with SB203580 (a p38MAPK inhibitor) or PD98059 (an ERK1/2 inhibitor), but not by SP600125 (a c‑jun N‑terminal kinase1/2/3 inhibitor), inhibited the TGF‑β1 stimulated CFB proliferation, as well as the elevation of α‑SMA and the deposition of type I and type III collagen, suggesting that ERK1/2 and p38MAPK signaling may be important in the in the process of myocardial fibrosis. In conclusion, the present study revealed that OMT treatment inhibited CFB proliferation and the CFB‑myofibroblast transition induced by TGF‑β1, at least in part through inhibition of ERK1/2 and p38MAPK signaling.