miR-17-5p Regulates Astrocyte Activation Through Targeting Mfn2 to Improve Nerve Function in Rats With Spinal Cord
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Spinal cord injury (SCI) is a severe and common form of central nervous system trauma, with the perilesional scar serving as a critical obstacle to SCI repair. While the role of miR-17-5p in SCI has been investigated, its influence on astrocyte activation and perilesional scar formation following SCI remains to be elucidated. In this study, we established an in vivo SCI model and an in vitro astrocyte activation model induced by mechanical injury. We explored the changes in motor function of rats and the expression levels of miR-17-5p in spinal cord tissues at multiple time points following SCI. The injury to spinal cord tissue, the distribution of astrocytes, and astrocyte proliferation following scratch injury were examined. The levels of inflammatory cytokines in both rat spinal cord tissues and astrocyte culture supernatants were quantified using ELISA. Additionally, the expression levels of miR-17-5p, mitofusin2 (Mfn2), and proteins associated with perilesional scarring in rat spinal cord tissue and astrocytes were evaluated at the molecular level. To verify the targeted regulatory relationship between miR-17-5p and Mfn2 in rat astrocytes, we employed the dual-luciferase reporter assay. The results demonstrated that the expression of miR-17-5p was significantly upregulated in the spinal cord of SCI rats, whereas the expression of Mfn2 was markedly downregulated. Upon silencing the expression of miR-17-5p in the spinal cord of SCI rats, neural function exhibited significant recovery. Furthermore, the downregulation of miR-17-5p effectively inhibited astrocyte activation, inflammatory responses, and perilesional scar formation. However, overexpression of miR-17-5p elicited opposing effects. Mfn2 was confirmed to be a downstream target gene of miR-17-5p. The upregulation of Mfn2 can partially counteract the promoting effects of miR-17-5p on astrocyte activation, proliferation, inflammatory response, and perilesional scar formation. In summary, miR-17-5p facilitates astrocyte activation and perilesional scarring through targeted suppression of Mfn2, consequently hindering the restoration of neural function in SCI rats.
