TGF-β1 inhibits the apoptosis of pulmonary arterial smooth muscle cells and contributes to pulmonary vascular medial thickening via the PI3K/Akt pathway.

Previous studies have highlighted that the transforming growth factor-β1 (TGF-β1) pathway may be activated by hypoxic conditions. TGF-β1 also participates in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. Furthermore, TGF-β1 has been reported to participate in the regulation of the progression of pulmonary arterial hypertension (PAH). However, the effect of TGF-β1 on pulmonary arterial smooth muscle cells (PASMCs) and the corresponding molecular mechanisms remain unclear. The present study aimed to determine whether TGF-β1 protects against cell apoptosis in PASMCs, and identify the underlying molecular mechanisms. Western blotting, MTT and lactate dehydrogenase activity assays were performed, and the activity of caspase-3 and caspase-9 was detected in order to investigate the hypothesis. It was determined that TGF-β1 may facilitate cell growth in a dose-dependent manner in serum-starved PASMCs. Furthermore, it was observed that apoptosis in serum-starved PASMCs was inhibited by TGF-β1 via regulation of the expression levels of mitochondrial membrane proteins. Additionally, the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway was found to be activated by TGF-β1 in PASMCs, while the inhibition of PI3K/Akt signaling also prevented the apoptosis-limiting effects of TGF-β1. These observations suggest that TGF-β1 protects PASMCs from apoptosis and contributes to pulmonary vascular medial thickening via the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]