title: MicroRNA-130a mediates proliferation of vascular smooth muscle cells in hypertension.
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.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Wu
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Zhang
authors.forename: Xian-Wei
authors.initials: XW
authors.lastname: Li
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xiong
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D006973:Hypertension / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
chemical_list: D018398:Homeodomain Proteins; C569198:MIRN130 microRNA, rat; C081336:Meox2 protein, rat; D035683:MicroRNAs; D009124:Muscle Proteins; D000804:Angiotensin II