title: MicroRNA 181b promotes vascular smooth muscle cells proliferation through activation of PI3K and MAPK pathways.
abstract: Vascular smooth muscle cells (VSMCs) hyperplasia is a common feature of pathologic cardiovascular event such as restenosis and atherosclerosis. The role and mechanisms of microRNAs (miRs) in VSMCs proliferation are poorly understood. Here, we report that miR-181b promotes VSMCs proliferation and migration. In an animal model, miR-181b was significantly increased in the rat carotid artery after balloon catheter injury. Delivery of miR-181b inhibitor to injured artery exhibited a marked inhibition of neointimal hyperplasia. Transfection of miR-181b with "mimics" to A10 cells accelerated cell proliferation, which was accompanied by an increase of cell migration. The induction of A10 cells proliferation by miR-181b appeared to be involved in activation of S and G2/M checkpoint, concomitant with decreases in cell-cycle inhibitors p21 and p27, and increases in cell-cycle activators CDK4 and cyclinD1. In contract, miR-181b inhibition attenuated A10 cells proliferation, inhibited cell migration and arrested cell cycle transition. Moreover, forced miR-181b expression elevated the phosphorylation levels of Akt and Erk1/2, whereas inhibition of miR-181b produced the opposite effects. Additionally, inhibition of PI3K and MAPK signaling pathways with specific inhibitors, but not inhibition of JNK pathway, significantly abolished the effects of miR-181b in promoting cell proliferation. These findings demonstrate that miR-181b enhances the proliferation and migration of VSMCs through activation of PI3K and MAPK pathways.
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Li
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Chao-Jun
authors.initials: CJ
authors.lastname: Gua
authors.affiliation: Ladder Molecular Biomedical Research Center Guangzhou 510800, China.
authors.forename: Sheng-Jiang
authors.initials: SJ
authors.lastname: Xue
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University Shenyang 110004, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000235:genetics; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: C581717:MIRN181 microRNA, rat; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases
keywords: Neointimal formation; miRNA-181b; proliferation; vascular smooth muscle cells