Upregulated miR-17 Regulates Hypoxia-Mediated Human Pulmonary Artery Smooth Muscle Cell Proliferation and Apoptosis by Targeting Mitofusin 2

摘要: BACKGROUND Pulmonary arterial hypertension (PAH) is a fatal disease characterized by impaired regulation of pulmonary artery vascular growth and remodeling. Aberrant expression miR-17 has been shown to be involved in the pathogenesis PAH, but its underlying molecular mechanism not elucidated. MATERIAL AND METHODS Mitofusin 2 (MFN2) was determined qRT-PCR. The protein levels MFN2, proliferating cell nuclear antigen (PCNA), pro-apoptotic cleaved Caspase-3 were measured using Western blot analysis. Cell proliferation apoptosis assessed CellTiter-Glo reagent flow cytometry, respectively. Caspase-3/7 activity an Apo-ONE Homogeneous assay kit. on MFN2 luciferase reporter system. RESULTS upregulated human smooth muscle cells (hPASMCs) treated with hypoxia lung tissues PAH patients. Inhibition suppressed hypoxia-induced promoted hPASMCs. inhibited binding 3'-UTR. Decreased viability increased observed anti-miR-17 + siNC group compared anti-miR-NC group. PCNA downregulated Moreover, these alterations attenuated knockdown MFN2. CONCLUSIONS regulates hPASMCs through modulation. We found that acts as potential regulator hPASMCs, it might developed promising new strategy for treatment PAH.