title: The microRNA miR-34c inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia by targeting stem cell factor.
abstract: The fine balance between proliferation and differentiation of vascular smooth muscle cells (VSMCs) is indispensable for the maintenance of healthy blood vessels, whereas an increase in proliferation participates in pathologic cardiovascular events such as atherosclerosis and restenosis. Here we report that microRNA-34c (miR-34c) targets stem cell factor (SCF) to inhibit VSMC proliferation and neointimal hyperplasia. In an animal model, miR-34c was significantly increased in the rat carotid artery after catheter injury. Transient transfection of miR-34c to either VSMCs or A10 cells inhibited cell survival by inducing apoptosis, which was accompanied by an increase in expression of p21, p27, and Bax. Transfection of miR-34c also attenuated VSMC migration. Bioinformatics showed that SCF is a target candidate of miR-34c. miR-34c down-regulated luciferase activity driven by a vector containing the 3'-untranslated region of SCF in a sequence-specific manner. Forced expression of SCF in A10 cells induced proliferation and migration, whereas knocking-down of SCF reduced cell survival and migration. miR-34c antagomir-induced VSMC proliferation was blocked by SCF siRNA. Delivery of miR-34c to rat carotid artery attenuated the expression of SCF and blocked neointimal hyperplasia. These results suggest that miR-34c is a new modulator of VSMC proliferation and that it inhibits neointima formation by regulating SCF.
authors: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors: Nakwon
authors: N
authors: Choe
authors: Division of Cardiovascular and Rare Disease, Korea National Institute of Health, Osong, Cheongju, Chungbuk 363-951, Republic of Korea.
authors: Jin-Sook
authors: JS
authors: Kwon
authors: Department of Cardiology, Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.
authors: Yong Sook
authors: YS
authors: Kim
authors: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors: Gwang Hyeon
authors: GH
authors: Eom
authors: Department of Cardiology, Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.
authors: Young Keun
authors: YK
authors: Ahn
authors: Department of Pharmacology, College of Medicine, Seonam University, Namwon 590-711, Republic of Korea.
authors: Yung Hong
authors: YH
authors: Baik
authors: Division of Cardiovascular and Rare Disease, Korea National Institute of Health, Osong, Cheongju, Chungbuk 363-951, Republic of Korea.
authors: Hyun-Young
authors: HY
authors: Park
authors: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea; Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea. Electronic address: kookhyun@chonnam.ac.kr.
authors: Hyun
authors: H
authors: Kook
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D002339:Carotid Arteries / Q000473:pathology*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D006965:Hyperplasia; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D058426:Neointima; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D019089:Stem Cell Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D050759:Cyclin-Dependent Kinase Inhibitor p21; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D019089:Stem Cell Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Atherosclerosis; Neointimal hyperplasia; Stem cell factor; Vascular smooth muscle cells; miR-34c