MicroRNA-130a Mediates Proliferation of Vascular Smooth Muscle Cells in Hypertension
MicroRNA-130a Mediates Proliferation of Vascular Smooth Muscle Cells in Hypertension
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MicroRNA-130a介导高血压血管平滑肌细胞增殖
DOI：
10.1038/ajh.2011.116
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发表时间：
2011-10-01
影响因子：
3.2
通讯作者：
Li, Yuan-Jian
中科院分区：
文献类型：
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作者：
Wu, Wei-Hua;Hu, Chang-Ping;Li, Yuan-Jian
研究背景已有报道microRNA-130 a（miR-130 a）靶向GAX，GAX是生长停滞特异性同源框，其抑制血管平滑肌细胞（VSMC）的增殖、分化和迁移。本研究采用5-溴-2 '-脱氧尿苷（5-bromo-2'-deoxyuridine，BrdU）掺入法检测miR-130 a对体外培养的VSMCs增殖的影响，探讨miR-130 a在高血压血管重构中的作用。采用定量逆转录-聚合酶链反应（RT-PCR）分析miR-130 a和GAX的表达。Western blot分析GAX蛋白表达。miR-130 a的模拟物和抑制剂分别用于体外功能获得和功能丧失研究。在自发性高血压大鼠（SHR）中观察到miR-130 a与血管重构的相关性，25或50 nmol/l的miR-130 a模拟物显著促进VSMCs增殖。miR-130 a在SHR主动脉和上级肠系膜动脉中表达上调。转染miR-130 a模拟物的VSMCs及SHR的胸主动脉和上级肠系膜动脉中GAX表达下调。血管紧张素II（Angiotensin II，Ang II）促进VSMCs增殖，上调miR-130 a表达，同时降低GAX表达，并呈浓度和时间依赖性。结论miR-130 a可能通过抑制GAX的表达而调节VSMCs的增殖，这可能与高血压时血管重构有关。
BACKGROUNDIt has been reported that microRNA-130a (miR-130a) targets GAX, the growth arrest-specific homeobox, which inhibits proliferation, differentiation, and migration of vascular smooth muscle cells (VSMCs). In the present study, we therefore investigated the effect of miR-130a on proliferation of cultured VSMCs and the potential role of miR-130a in vascular remodeling during hypertension.METHODSProliferation of VSMCs was determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation method. The expression of miR-130a and GAX was analyzed by quantitative reverse transcription-PCR. The protein expression of GAX was analyzed by western blot. The mimic and inhibitor of miR-130a were used in gain-of-function and loss-of-function in vitro studies, respectively. The correlation of miR-130a with vascular remodeling was observed in spontaneously hypertensive rats (SHRs).RESULTSMiR-130a mimic at the concentration of 25 or 50 nmol/l significantly promoted proliferation of VSMCs. The expression of miR-130a was upregulated in the remodeled aorta and superior mesenteric artery of SHRs. The expression of GAX was downregulated in VSMCs transfected with miR-130a mimic and in thoracic aorta and superior mesenteric artery of SHRs. Angiotensin II (Ang II) promoted proliferation of VSMCs and upregulated miR-130a expression concomitantly with a decreased GAX expression in a concentration and time-dependent manner. The proliferative effects of Ang lion VSMCs were suppressed partly by the miR-130a inhibitor.CONCLUSIONSThese results suggest that miR-130a is a novel regulator of proliferation of VSMCs via inhibiting the expression of GAX, which may contribute to vascular remodeling in hypertension.