1. MicroRNA-130a mediates proliferation of vascular smooth muscle cells in hypertension
- Author
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Yuan-Jian Li, Xian-Wei Li, Chang-Ping Hu, Xiao-Ming Xiong, Wei-Hua Wu, Wei-Fang Zhang, and Xiao-Ping Chen
- Subjects
Male ,medicine.medical_specialty ,Vascular smooth muscle ,Myocytes, Smooth Muscle ,Muscle Proteins ,Rats, Inbred WKY ,Muscle, Smooth, Vascular ,Rats, Sprague-Dawley ,Downregulation and upregulation ,Western blot ,Internal medicine ,medicine.artery ,Rats, Inbred SHR ,Internal Medicine ,medicine ,Myocyte ,Animals ,Superior mesenteric artery ,Cells, Cultured ,Cell Proliferation ,Homeodomain Proteins ,Aorta ,medicine.diagnostic_test ,Cell growth ,business.industry ,Angiotensin II ,Rats ,MicroRNAs ,Endocrinology ,Hypertension ,cardiovascular system ,Cardiology ,business - Abstract
Background It 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. Methods Proliferation 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). Results MiR-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 II on VSMCs were suppressed partly by the miR-130a inhibitor. Conclusions These 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.
- Published
- 2011