Journal
NEUROSCIENCE LETTERS
Volume 759, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2021.135947
Keywords
GRP78; Endoplasmic reticulum stress; Seipin; miR-187-3p; Cerebral ischemia
Categories
Funding
- National Natural Science Foundation of China [81360199]
- Special Grant for Central Government Supporting Local Science and Technology Development, Science and Technology Department of Guizhou Province, China [(2019) 4008]
- Science and Technology Plan Project of Guizhou Province (Basic Science and Technology Cooperation) , China [(2020) 1Z060]
- Science and Technology Fund Project of Guizhou Health and Health Commission, China [gzwjkj20191039]
- Science and Technology Fund Project of Southwest Guizhou Autonomous Prefecture, China [2019110]
- Basic Science Technology Project of Guizhou Province, China [ZK [2021] 412]
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The study revealed that miR-187-3p plays a regulatory role in I/R injury by modulating the seipin-mediated ERS pathway. The increase in miR-187-3p and decrease in seipin expression were closely associated with I/R-induced ERS.
Ischemia/reperfusion (I/R) injury induces activation of the endoplasmic reticulum stress (ERS) pathway, accompanied by an increase in apoptosis. Multiple microRNAs (miRNAs/miRs) are dysregulated during I/R and contribute to I/R-induced injury. miRNAs act as suppressors of gene expression and negatively regulate gene expression by targeting the protein-coding sequence (CDS) of specific target mRNAs. Seipin is an endoplasmic reticulum protein that has recently been associated with ERS. We previously reported that seipin is the target gene of miR-187-3p. Therefore, we explored the involvement of miR-187-3p in I/R-induced ERS via the regulation of seipin. A rat MCAO/R model was established by 1 h of occlusion and 24 h reperfusion. Neurological deficits and infarction area were examined. PC12 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to model I/R. Expression levels of miR-187-3p and proteins related to ERS and apoptosis were measured using RT-PCR, western blotting, immunofluorescence, and immunohistochemistry, respectively. TUNEL staining was used to assay apoptosis. MCAO/R-induced morphological changes were analyzed with Nissl staining and Hematoxylin-eosin staining. I/R-induced ERS was closely associated with an increase in miR-1873p and a decrease in seipin expression. miR-187-3p agomir further activated the ERS pathway and promoted apoptosis but decreased seipin expression levels; these effects were reversed by miR-187-3p antagomir. Moreover, seipin knockdown aggravated ERS in PC12 cells after OGD/R, and this change was rescued by seipin overexpression. miR-187-3p antagomir did not suppress ERS and apoptosis in seipin knockdown PC12 cells after OGD/R. Our findings demonstrate that the inhibition of miR-187-3p attenuated I/R-induced cerebral injury by regulating seipin-mediated ERS.
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