microRNA-195 attenuates neuronal apoptosis in rats with ischemic stroke through inhibiting KLF5-mediated activation of the JNK signaling pathway

• Published in: Molecular medicine (Cambridge, Mass.) Mass.), 2020-04, Vol.26 (1), p.31-31
• Main Authors: Chang, Lisha, Zhang, Wan, Shi, Songxin, Peng, Yanbo, Wang, Dali, Zhang, Li, Zhang, Jiang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Brain; Cancer; Carotid arteries; Cell Survival; Cells, Cultured; Dehydrogenases; Disease Models, Animal; Gene Expression Regulation; Gene Knockout Techniques; Ischemia; Ischemic stroke; Ischemic Stroke - genetics; Ischemic Stroke - metabolism; JNK signaling pathway; Kinases; KLF5; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Laboratory animals; Male; MAP Kinase Signaling System; microRNA-195; MicroRNAs; MicroRNAs - genetics; Neurons - cytology; Neurons - metabolism; Plasticity; Rats; Rodents; Stroke; Veins & arteries
• ISSN: 1076-1551; 1528-3658
• DOI: 10.1186/s10020-020-00150-w

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. 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. 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. 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.