Cytosolic free Ca2+ concentration is a key factor in pulmonary vasoconstriction 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 Ca2+ influx under both normoxia and hypoxia. These findings indicate miR-429 and miR-424-5p target CaSR and may function as Ca2+ influx suppressors in pulmonary arterial hypertension-associated diseases.

中文翻译：

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miR-429和miR-424-5p通过下调肺动脉平滑肌细胞中的CaSR来抑制细胞增殖和Ca2+内流

胞浆游离钙2+浓度是肺血管收缩和肺动脉平滑肌细胞（PASMC）血管重塑的关键因素。这些过程会导致肺动脉高压，并受到钙敏感受体 (CaSR) 表达的影响。尽管 CaSR 表达的调节受到精确控制，但 microRNA (miR) 的贡献尚不完全清楚。在这里，我们证明 miR-429、miR-424-5p、miR-200b-3p 和 miR-200c-3p 通过靶向特定的 3'-非翻译区来调节 CaSR，表明这些 miRNA 在 PASMC 中充当 CaSR 抑制剂。此外，miR-429和miR-424-5p通过下调CaSR抑制PASMCs的增殖，导致CaSR减少2+在常氧和缺氧情况下都会涌入。这些发现表明 miR-429 和 miR-424-5p 靶向 CaSR，并可能作为 Ca2+肺动脉高压相关疾病中的流入抑制因子。