MicroRNA-137 Inhibited Hypoxia-Induced Proliferation of Pulmonary Artery Smooth Muscle Cells by Targeting Calpain-2.
MicroRNA-137 Inhibited Hypoxia-Induced Proliferation of Pulmonary Artery Smooth Muscle Cells by Targeting Calpain-2.
复制标题
MicroRNA-137 通过靶向 Calpain-2 抑制缺氧诱导的肺动脉平滑肌细胞增殖
DOI：
10.1155/2021/2202888
复制
发表时间：
2021
影响因子：
--
通讯作者：
Hu CP
中科院分区：
文献类型：
--
作者：
Ge XY;Zhu TT;Yao MZ;Liu H;Wu Q;Qiao J;Zhang WF;Hu CP
肺动脉平滑肌细胞(PASMCs)的增殖是肺动脉高压(PH)肺血管重构的重要原因。已有研究表明miR-137可抑制肿瘤细胞的增殖。然而，miR-137是否参与了PH尚不清楚。本研究将雄性SD大鼠置于10%O2中3周建立PH模型，并用低氧(3%O2)处理大鼠原代PASMC 48 h以诱导细胞增殖。通过转染miR-137模拟物和抑制物检测miR-137对PASMC增殖和Calain-2表达的影响。通过转染calain-2 siRNA检测calain-2对PASMC增殖的影响。本研究首次发现miR-137在低氧大鼠的肺动脉和低氧处理的PASMCs中表达下调。MIR-137模拟抑制低氧诱导的PASMC增殖和上调CaPain-2的表达。此外，miR-137抑制剂可诱导常氧条件下PASMCs的增殖，siRNA下调calain-2mRNA可显著抑制缺氧诱导的PASMCs的增殖。我们的研究表明，缺氧诱导的miR-137表达下调通过靶向calain-2促进PASMCs的增殖，从而可能导致缺氧性PH肺血管重构。
The proliferation of pulmonary artery smooth muscle cells (PASMCs) is an important cause of pulmonary vascular remodeling in pulmonary hypertension (PH). It has been reported that miR-137 inhibits the proliferation of tumor cells. However, whether miR-137 is involved in PH remains unclear. In this study, male Sprague-Dawley rats were subjected to 10% O2 for 3 weeks to establish PH, and rat primary PASMCs were treated with hypoxia (3% O2) for 48 h to induce cell proliferation. The effect of miR-137 on PASMC proliferation and calpain-2 expression was assessed by transfecting miR-137 mimic and inhibitor. The effect of calpain-2 on PASMC proliferation was assessed by transfecting calpain-2 siRNA. The present study found for the first time that miR-137 was downregulated in pulmonary arteries of hypoxic PH rats and in hypoxia-treated PASMCs. miR-137 mimic inhibited hypoxia-induced PASMC proliferation and upregulation of calpain-2 expression in PASMCs. Furthermore, miR-137 inhibitor induced the proliferation of PASMCs under normoxia, and knockdown of calpain-2 mRNA by siRNA significantly inhibited hypoxia-induced proliferation of PASMCs. Our study demonstrated that hypoxia-induced downregulation of miR-137 expression promoted the proliferation of PASMCs by targeting calpain-2, thereby potentially resulting in pulmonary vascular remodeling in hypoxic PH.
登录
查看更多内容
影响因子：
9.6
作者：
Dunham-Snary, Kimberly J.;Wu, Danchen;Archer, Stephen L.
通讯作者：
Archer, Stephen L.
DOI：
10.1152/ajplung.00260.2016
发表时间：
2017-05-01
影响因子：
4.9
作者：
Cai, Pengcheng;Kovacs, Laszlo;Su, Yunchao
通讯作者：
Su, Yunchao
影响因子：
5.5
作者：
Meloche, Jolyane;Le Guen, Marie;Bonnet, Sebastien
通讯作者：
Bonnet, Sebastien
影响因子：
11.2
作者：
Kozaki, Ken-ichi;Imoto, Issei;Inazawa, Johji
通讯作者：
Inazawa, Johji
DOI：
10.1164/rccm.201812-2290oc
发表时间：
2019-09-01
影响因子：
24.7
作者：
Kovacs, Laszlo;Cao, Yapeng;Su, Yunchao
通讯作者：
Su, Yunchao