β-Arrestins1 inhibit autophagy induced by hypoxic injury in human pulmonary artery endothelial cells via Akt/mTOR signaling pathway

Background To investigate the potential effects of β-Arrestins1 on autophagy and apoptosis in human pulmonary artery endothelial cells (hPAECs) under hypoxic stress. Methods The hPAECs were exposed to normoxic condition and hypoxic injury for 24 h, 48 h, and 72 h, respectively. Then, to explore effects of autophagy on hPAECs with hypoxia, cells were administrated with 3-MA (an inhibitor autophagy). β-Arrestins1 was regulated to explore its effects on autophagy and apoptosis of hPAECs. Transwell cell migration assay and scratch assay were performed to detect the migration by light microscope. Then, CCK-8 assay was used to investigate the proliferation of hPAECs. Meanwhile, TUNEL assay served as apoptosis in hPAECs. In addition, Western blotting assay applied to evaluate protein expressions. Results Hypoxia contributed to hyperproliferation, migration apoptosis resistance of hPAECs. Meanwhile, autophagy was increased in hypoxic hPAECs. Excessive proliferation、migration and apoptosis resistance of hPAECs were reversed after inhibition of autophagy. Then, the β-Arrestins1 and VEGFR3 expression levels were decreased in hypoxic conditions. Moreover, the activity of Akt/mTOR signal pathway was restrained after hypoxic injury. At last, β-Arrestins1+/+ repressed the increased autophagy and apoptosis resistance of hPAECs under hypoxia. Conclusions Our study indicated that β-Arrestins1 mediated VEGFR3 reduced excessive autophagy and apoptosis resistance via Akt/mTOR pathway of hPAECs under hypoxia. It may provide a promising therapeutic target for pulmonary artery hypertension (PAH).