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

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Abstract

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-1α, 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 α-smooth muscle actin (SM-α-actin), Myocardin, smooth muscle myosin heavy chain (SMMHC), and smooth muscle-22α (SM22α), Calponin1 and Hypoxia-inducible factor-1α(HIF-1α), 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-1α 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-1α.

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Acknowledgements

The work was supported by Major projects of Natural Science Research in Colleges and Universities of Anhui Province (No. KJ2018ZD023), The Natural Science Foundation of Anhui province (No. 1908085QH353) and Anhui Province Education Key Projects (No. SK2018A1069).

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Correspondence to Pin-fang Kang.

Additional information

Corresponding editor: Gagandeep Kang

Communicated by GAGANDEEP KANG.

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Tang, B., Tang, M., Xu, Q. et al. MicroRNA-143–5p modulates pulmonary artery smooth muscle cells functions in hypoxic pulmonary hypertension through targeting HIF-1α. J Biosci 45, 37 (2020). https://doi.org/10.1007/s12038-020-9992-1

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Keywords

  • MicroRNA-143–5p
  • pulmonary artery smooth muscle cells
  • hypoxic pulmonary hypertension
  • HIF-1α