title: MicroRNA-493 regulates angiogenesis in a rat model of ischemic stroke by targeting MIF.
abstract: MicroRNA-493 (miR-493) is known to suppress tumour metastasis and angiogenesis and its expression is decreased in stroke patients. In the present study, we investigated a role for miR-493 in regulating post-stroke angiogenesis. We found decreased expression of miR-493 in the ischemic boundary zone (IBZ) of rats subjected to middle cerebral artery occlusion (MCAO), and in rat brain microvascular endothelial cells (RBMECs) exposed to oxygen glucose deprivation. Down-regulating miR-493 with a lateral ventricular injection of antagomir-493, a synthetic miR-493 inhibitor, increased capillary density in the IBZ, decreased focal infarct volume and ameliorated neurologic deficits in rats subjected to MCAO. Intriguingly, MCAO also increased the expression of macrophage migration inhibitory factor (MIF) in the IBZ of rats; MIF expression was also increased in RBMECs exposed to oxygen glucose deprivation. We found that miR-493 directly targeted MIF, and that the protective effect of miR-493 inhibition in angiogenesis was attenuated by knocking down MIF. This effect could then be rescued by administration of recombinant MIF. Our findings highlight the importance of miR-493 in regulating angiogenesis after MCAO, and indicate that miR-493 is a potential therapeutic target in the treatment of stroke.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Quanwei
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Suraj
authors.initials: S
authors.lastname: Baral
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shengcai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tianhui
authors.initials: T
authors.lastname: An
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yuanpeng
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002561:Cerebrovascular Disorders / Q000601:surgery; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020768:Middle Cerebral Artery / Q000601:surgery; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010100:Oxygen / Q000494:pharmacology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020521:Stroke / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: D000070416:Antagomirs; C000620780:MIRN-493 microRNA, rat; D008263:Macrophage Migration-Inhibitory Factors; D035683:MicroRNAs; D034741:RNA, Small Interfering; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat; D005947:Glucose; D010100:Oxygen
keywords: Akt/ERK; MIF; angiogenesis; ischemia; miR-493