title: Let-7a gene knockdown protects against cerebral ischemia/reperfusion injury.
abstract: The microRNA (miRNA) let-7 was one of the first miRNAs to be discovered, and is highly conserved and widely expressed among species. let-7 expression increases in brain tissue after cerebral ischemia/reperfusion injury; however, no studies have reported let-7 effects on nerve injury after cerebral ischemia/reperfusion injury. To investigate the effects of let-7 gene knockdown on cerebral ischemia/reperfusion injury, we established a rat model of cerebral ischemia/reperfusion injury. Quantitative reverse transcription-polymerase chain reaction demonstrated that 12 hours after cerebral ischemia/reperfusion injury, let-7 expression was up-regulated, peaked at 24 hours, and was still higher than that in control rats after 72 hours. Let-7 gene knockdown in rats suppressed microglial activation and inflammatory factor release, reduced neuronal apoptosis and infarct volume in brain tissue after cerebral ischemia/reperfusion injury. Western blot assays and luciferase assays revealed that mitogen-activated protein kinase phosphatase-1 (MKP1) is a direct target of let-7. Let-7 enhanced phosphorylated p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) expression by down-regulating MKP1. These findings suggest that knockdown of let-7 inhibited the activation of p38 MAPK and JNK signaling pathways by up-regulating MKP1 expression, reduced apoptosis and the inflammatory reaction, and exerted a neuroprotective effect following cerebral ischemia/reperfusion injury.
authors.affiliation: Department of Neurology, First Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Zhong-Kun
authors.initials: ZK
authors.lastname: Wang
authors.affiliation: Department of Neurology, Jilin Central Hospital, Jilin, Jilin Province, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Liu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, the Second Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, First Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Xin-Mei
authors.identifier: 0000-0001-7892-3276
authors.initials: XM
authors.lastname: Jiang
authors.affiliation: Department of Neurology, First Hospital, Jilin University, Changchun, Jilin Province, China.
authors.forename: Xue-Fan
authors.identifier: 0000-0002-0581-7234
authors.initials: XF
authors.lastname: Yu
keywords: apoptosis; brain injury; c-Jun N-terminal kinase; cerebral ischemia/reperfusion injury; gene knockdown; inflammation; let-7; microglia; mitogen-activated protein kinase; mitogen-activated protein kinase phosphatase-1; nerve regeneration; neural regeneration; neurons