MiR-429 and miR-424-5p inhibit cell proliferation and ca 2+ influx by downregulating casr in pulmonary artery smooth muscle cells

Abstract

November 21, 2018; doi:10.1152/ajpcell.00219.2018.—Cyto-solic free Ca 2+ concentration is a key factor in pulmonary vasocon-striction and vascular remodeling of pulmonary artery smooth muscle cells (PASMCs). These processes contribute to pulmonary arterial hypertension and are influenced by expression of calcium-sensing receptor (CaSR). Although regulation of CaSR expression is precisely controlled, the contribution of microRNAs (miR) is incompletely understood. Here, we demonstrate that miR-429, miR-424-5p, miR-200b-3p, and miR-200c-3p regulate CaSR by targeting specific 3'-untranslated region, suggesting that these miRNAs function as CaSR inhibitors in PASMCs. Moreover, miR-429 and miR-424-5p inhibit proliferation of PASMCs by downregulating CaSR, resulting in reduced Ca 2+ influx under both normoxia and hypoxia. These findings indicate miR-429 and miR-424-5p target CaSR and may function as Ca 2+ influx suppressors in pulmonary arterial hypertension-associ-ated diseases.