title: Neuroprotective effects of viral overexpression of microRNA-22 in rat and cell models of cerebral ischemia-reperfusion injury.
abstract: Several studies have reported that microRNA (MIR) is involved in the pathogenesis and progression of ischemic diseases, including cerebral ischemia, and that MIR-22 may inhibit the inflammatory response and cell apoptosis, which contribute to ischemia/reperfusion (I/R) injury. However, the specific function of MIR-22 in cerebral I/R injury remains far from clear. This study aimed to examine the potential protective effect of MIR-22 against cerebral I/R injury and its mechanism. As predicted, adenovirus-mediated MIR-22 overexpression markedly reduced the neurological score and infarct size (P < 0.05). We demonstrated that MIR-22 overexpression resulted in a reduction in inflammatory cytokines TNF-α, IL-6, COX-2, and iNOS, whereas the level of IL-10 was enhanced. MIR-22 overexpression significantly inhibited NF-κB activity by decreasing NF-κB coactivator NCOA1 expression. Furthermore, we found that MIR-22 could reduce the apoptotic rate of cortical neurons. Caspase-3 activity was inhibited by MIR-22, and the expression of the anti-apoptosis gene Bcl-2 in neurons was increased and that of the pro-apoptosis gene Bax decreased following MIR-22 overexpression. Our results suggest that MIR-22 could be used to treat cerebral I/R injury and that its neuroprotective effect may be attributed to a reduction in inflammation and apoptosis.
authors.affiliation: Department of Emergency Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032,, China.
authors.forename: Houyou
authors.initials: H
authors.lastname: Yu
authors.forename: Mingchun
authors.initials: M
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Yin
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1 / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C580892:MIRN22 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D056920:Nuclear Receptor Coactivator 1; D053148:Caspase 3
keywords: APOPTOSIS; CEREBRAL ISCHEMIA/REPERFUSION INJURY; INFLAMMATORY; microRNA-22