MicroRNA-150 relieves vascular remodeling and fibrosis in hypoxia-induced pulmonary hypertension - 09/12/18
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Highlights |
• | MiR-150 alleviates increased pulmonary arterial pressure and vascular remodeling in rats with PH. |
• | MiR-150 inhibits hypoxia-induced pulmonary fibrosis in vivo and in vitro. |
• | MiR-150 restrains proliferation and induces apoptosis in PASMCs after exposure to hypoxia. |
• | MiR-150 represses hypoxia-induced NFATc3 expression in vivo and in vitro. |
• | MiR-150 restrains proliferation and induces apoptosis in PAECs after exposure to hypoxia. |
Abstract |
Pulmonary hypertension (PH) is a dangerous disease, featured by pulmonary vascular remodeling. Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs) plays crucial roles in this process. MicroRNA-150 (miR-150) level has been found to be reduced in patients with PH, and correlated with the poor survival. This study aimed to investigate the beneficial effect of miR-150 on PH in hypoxia-induced rats, PASMCs and PAECs. The results showed that miR-150 level was reduced in the lung tissue and plasma of hypoxia-treated rats. Lentivirus-mediated overexpression of miR-150 restrained hypoxia-induced increase in right ventricular systolic pressure and decrease in cardiac output. Moreover, as assessed by HE staining, hypoxia-induced thickening of vessel wall was relieved by miR-150 up-regulation. Overexpression of miR-150 also suppressed hypoxia-induced formation of collagen fiber, expressions of α-SMA, TGF-β1, and collagen I in lung tissues and PASMCs. In addition, the excessive proliferation of PASMCs induced by hypoxia was repressed by miR-150 overexpression via AKT/mTOR signaling pathway. Increased NFATc3 expression in response to hypoxia was restrained by miR-150 overexpression in lung tissue and PAMSCs. Finally, miR-150 overexpression inhibited hypoxia-induced proliferation and apoptosis resistance in PAECs. In conclusion, these results indicate that miR-150 protects against hypoxia-induced pulmonary vascular remodeling, fibrosis, abnormal proliferation of PASMCs and PAECs, which suggests miR-150 as a promising therapeutic target for PH.
Le texte complet de cet article est disponible en PDF.Keywords : microRNA-150, Pulmonary hypertension, Vascular remodeling, Fibrosis, Pulmonary artery smooth muscle cells, Pulmonary artery endothelial cells
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