Author:
Chang Lisha,Zhang Wan,Shi Songxin,Peng Yanbo,Wang Dali,Zhang Li,Zhang Jiang
Abstract
Abstract
Background
Accumulating evidence has implicated the regulation of microRNAs (miRs) in ischemia stroke. The current study aimed to elucidate the role of microRNA-195 (miR-195) in neuronal apoptosis and brain plasticity in rats with ischemic stroke via the JNK signaling pathway/KLF5 axis.
Methods
Ischemic stroke rat models were established by middle cerebral artery occlusion (MCAO), and oxygen deprivation (OGD) models were constructed in rat neuronal cells, followed by gain- or loss-of-function of miR-195 and/or KLF5 in rats and cells. Infarct volume, neuronal loss and ultrastructure, the expression of GAP-43, SYP and KLF5 protein as well as cell apoptosis were determined in the rats. Caspase-3 activity as well as the expression of miR-195, KLF5, GAP-43, SYP, JNK, phosphorylated JNK, Bax and Bcl-2 was measured in the cells.
Results
The infarct size, expression of GAP-43 and SYP protein and apoptotic cells were increased in the miR-195−/− MCAO rats, while reductions were detected in the miR-195 mimic MCAO and KLF5−/− MCAO rats. Bcl-2 expression was increased, Bax and Caspase-3 expression as well as the ratio of phosphorylated JNK/JNK was decreased in response to miR-195 overexpression or KLF5 knockdown. Interestingly, the silencing of KLF5 reversed the effects exerted by the miR-195 inhibitor on the expression of Bcl-2, phosphorylated JNK/JNK, Bax and Caspase-3.
Conclusions
Collectively, our study unraveled that miR-195 could down-regulate KLF5 and block the JNK signaling pathway, ultimately inhibiting neuronal apoptosis in rats with ischemic stroke.
Publisher
Springer Science and Business Media LLC
Subject
Genetics(clinical),Genetics,Molecular Biology,Molecular Medicine
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