Affiliation:
1. Department of Anesthesiology, Zhongnan Hospital of Wuhan University, China
Abstract
Objective. Inflammation and oxidative stress are implicated in the pathogenesis of spinal cord injury (SCI). The present study is aimed at investigating the function and molecular basis of microRNA-299a-5p (miR-299a-5p) during SCI in mice. Methods. Mice were exposed to SCI surgery and then intrathecally injected with the agomir, antagomir, or matched negative controls of miR-299a-5p to overexpress or silence miR-299a-5p. To inhibit AMP-activated protein kinase (AMPK), mice were intraperitoneally injected with compound C (CC). To overexpress pH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), lentiviral vectors were used. Results. The miR-299a-5p expression in the spinal cord was dramatically reduced by SCI stimulation. The miR-299a-5p agomir prevents, while the miR-299a-5p antagomir exacerbates inflammation, oxidative stress, and SCI in mice. Mechanistically, we found that miR-299a-5p directly inhibited PHLPP1 and subsequently activated AMPK pathway. The PHLPP1 overexpression of AMPK inhibition with either genetic or pharmacologic methods dramatically abolished the miR-299a-5p agomir-mediated protective effects against SCI. Conclusion. miR-299a-5p protects against spinal cord injury through activating AMPK pathway.
Subject
Cell Biology,Aging,General Medicine,Biochemistry
Cited by
3 articles.
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