MicroRNA-143-5p modulates pulmonary artery smooth muscle cells functions in hypoxic pulmonary hypertension through targeting HIF-1α

This paper explores the potential mechanism of microRNA-143-5p regulation effects on pulmonary artery smooth muscle cells (PASMCs) functions in hypoxic pulmonary hypertension (HPH) via targeting HIF-1 alpha, which may offer a new idea for HPH therapy. PASMCs were transfected with mimics control/miR-143-5p mimics or inhibitor control/miR-143-5p inhibitor. We used Western blotting and RT-qPCR to detect the protein and mRNA expressions, CCK-8 assay to detect cellular viability, Annexin V-FITC/PI staining and caspase-3/cleaved caspase-3 protein to evaluate cellular apoptosis, transwell migration experiment for cellular migration measurement and Dual luciferase reporter gene assay to prove the target of miR-143-5p. Cells under hypoxic condition presented the decreased protein and mRNA expressions of alpha -smooth muscle actin (SM-alpha -actin), Myocardin, smooth muscle myosin heavy chain (SMMHC), and smooth muscle-22 alpha (SM22 alpha), Calponin1 and Hypoxia-inducible factor-1 alpha (HIF-1 alpha), the increased cell viability and miR-143-5p level; Over-expression of miR-143-5p obviously reduced vascular smooth muscle-specific contraction marker protein levels and cellular apoptosis, increased cellular migration of PASMCs with hypoxia stimulation; Low-expression of miR-143-5p caused the opposite changes, while co-transfected with Si HIF-1 alpha blocked the beneficial effects of miR-143-5p inhibition on PASMCs under hypoxia. MicroRNA-143-5p can promote the phenotype conversion, proliferation and migration of pulmonary artery smooth muscle cells under hypoxic condition through direct targeting of HIF-1 alpha.