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MicroRNA-155 induces protection against cerebral ischemia/reperfusion injury through regulation of the Notch pathway in vivo
microRNA (miR)-155 has been demonstrated to participate in the regulation of endothelium during cerebral ischemia. In the present study, it was aimed to investigate the molecular mechanism of miR-155 in the regulation of cerebral ischemia/reperfusion (I/R) injury with middle cerebral artery occlusio...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566036/ https://www.ncbi.nlm.nih.gov/pubmed/31258696 http://dx.doi.org/10.3892/etm.2019.7590 |
Sumario: | microRNA (miR)-155 has been demonstrated to participate in the regulation of endothelium during cerebral ischemia. In the present study, it was aimed to investigate the molecular mechanism of miR-155 in the regulation of cerebral ischemia/reperfusion (I/R) injury with middle cerebral artery occlusion (MCAO) in mice. The MCAO model was established in C57BL/6 mice. Transfection of miR-155 mimics and miR-155 inhibitors was performed to alter the expression of miR-155. The level of miR-155 was measured by RT-qPCR analysis. The western blotting results demonstrated that deletion of miR-155 increased the expression of Notch1, intracellular Notch receptor domain (NICD) and hairy and enhancer of split-1 (Hes1) levels. In addition, the percentage of terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling-positive cells and caspase-3 levels were decreased following treatment with a miR-155 inhibitor compared with the Pre-IR group. Notably, disrupting miR-155 also increased nitric oxide (NO) production and the expression of endothelial NO synthase (eNOS), leading to downregulation of brain water content and Evans blue levels. However, overexpression of miR-155 restored all these changes to similar levels observed in the cerebral I/R injury group. The expressions of Notch1, NICD and Hes1 were also decreased to the cerebral I/R injury condition. In conclusion, a novel mechanism was identified for abrogating normal NO production and eNOS expression via the aberrant expression of the Notch signaling pathway, a mechanism that may be modulated by miR-155. Together, these results reveal important functions of miR-155 in regulating the Notch signaling pathway of the nervous system, and a potential role for miR-155 as a crucial therapy target for cerebral stroke. |
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