title: MicroRNA-29b is a therapeutic target in cerebral ischemia associated with aquaporin 4.
abstract: MicroRNA-29b (miR-29b) is involved in regulating ischemia process, but the molecular mechanism is unclear. In this work, we explored the function of miR-29b in cerebral ischemia. The level of miR-29b in white blood cells was evaluated in patients and mice after ischemic stroke. Brain infarct volume and National Institute of Health stroke scale (NIHSS) scores were analyzed to determine the relationship between miR-29b expression and the severity of stroke. The relationship of miR-29b and aquaporin-4 (AQP4) was further studied in mice. We found that miR-29b was significantly downregulated in stroke patients (P<0.05). MiR-29b level negatively associated with NIHSS scores (r=-0.349, P<0.01) and brain infarct volume (r=-0.321, P<0.05). In ischemic mice, miR-29b in the brain and blood were both downregulated (r=0.723, P<0.05). MiR-29b overexpression reduced infarct volume (49.50±6.55 versus 35.48±2.28 mm(3), P<0.05), edema (164±4% versus 108±4%, P<0.05), and blood-brain barrier (BBB) disruption compared with controls (15±9% versus 7±3%, P<0.05). Aquaporin-4 expression greatly decreased after miR-29b overexpression (28±7% versus 11±3%, P<0.05). Dual-luciferase reporter system showed that AQP-4 was the direct target of miR-29b (P<0.05). We concluded that miR-29b could potentially predict stroke outcomes as a novel circulating biomarker, and miR-29b overexpression reduced BBB disruption after ischemic stroke via downregulating AQP-4.
authors.affiliation: Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yongting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Ouyang
authors.affiliation: Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics*; D015415:Biomarkers; D001812:Blood-Brain Barrier / Q000473:pathology; D001929:Brain Edema / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics*; D002544:Cerebral Infarction / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000097:blood / Q000187:drug effects / Q000235:genetics*; D011237:Predictive Value of Tests; D020521:Stroke / Q000188:drug therapy / Q000235:genetics
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D015415:Biomarkers; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs