miR-320-3p regulates the proliferation, migration and apoptosis of hypoxia-induced pulmonary arterial smooth muscle cells via KLF5 and HIF1α.
miR-320-3p regulates the proliferation, migration and apoptosis of hypoxia-induced pulmonary arterial smooth muscle cells via KLF5 and HIF1α.
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发表时间：
2021
影响因子：
2.2
通讯作者：
Dandan Ding;Hongxia Jiang;Yuanzhou He;Xiaochen Li;Xiansheng Liu
中科院分区：
文献类型：
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作者：
Dandan Ding;Hongxia Jiang;Yuanzhou He;Xiaochen Li;Xiansheng Liu
不可逆性肺动脉高压(PH)主要由血管重塑引起，其中肺动脉平滑肌细胞(PASMCs)的异常生长起着重要作用。我们以前的工作表明，KLF5和HIF1α与缺氧性PH的发病机制密切相关，因为它们参与了PASMC的生长。MicroRNAs(MiRNAs)已被证明参与控制细胞的增殖和凋亡。在本研究中，我们检测了与KLF5相关的6个miRNAs在低氧大鼠PH模型和PASMCs中的表达，并进一步探讨了miR-320-3p在缺氧性PASMCs异常增殖中的作用以及在缺氧性PASMCs的进展和治疗结果中的作用。结果表明，miR-320-3p在缺氧性大鼠肺动脉高压模型、缺氧性PASMCs和慢性血栓栓塞性肺动脉高压(CTEPH)患者中表达下调。此外，miR320-3p还直接调控KLF5和HIF1α的表达。MIR-320-3p模拟物抑制缺氧PASMCs的增殖和迁移，促进细胞凋亡。KLF5和HIF1α可逆转miR-320-3P的上述作用。结论：miR-320-3p通过KLF5和HIF1α在缺氧性肺高压的发生发展中起一定作用，有望成为治疗低氧性肺高压的有效手段。
Irreversible pulmonary hypertension (PH) mainly results from vascular remodeling, in which the aberrant growth of pulmonary arterial smooth muscle cells (PASMCs) plays a significant role. Our previous work suggested that KLF5 and HIF1α are closely associated with the pathogenesis of hypoxic PH as they intervene in the growth of PASMCs. MicroRNAs (miRNAs) have been demonstrated to be involved in the control of cell proliferation and apoptosis. In the present study, we detected the expression of six miRNAs connected with KLF5 in hypoxia-exposed rat PH models and PASMCs and then further investigated the role of miR-320-3p in the abnormal proliferation of hypoxic PASMCs and in the progression and treatment outcomes of hypoxia-induced PH. The results indicated that miR-320-3p was downregulated in hypoxia-exposed rat PH models, hypoxia-induced PASMCs and chronic thromboembolic pulmonary hypertension (CTEPH) patients. Moreover, miR-320-3p directly regulated the expression of KLF5 and HIF1α. miR-320-3p mimics inhibited proliferation and migration and promoted apoptosis in hypoxic PASMCs. KLF5 and HIF1α reversed the above effects of miR-320-3p. In conclusion, miR-320-3p plays a certain role in the progression of hypoxic PH via KLF5 and HIF1α and might be a potent therapeutic tool for PH.