What type of study is this?

This is a In Vitro Study study (also classified as: Animal Study).

September 23, 2025

miR‐17‐5p Regulates Astrocyte Activation Through Targeting Mfn2 to Improve Nerve Function in Rats With Spinal Cord Injury

YZYan ZhaoWuhan Puai Hospital HWHan WuCapital Medical University MXMeixia XuWuhan Puai Hospital

Key Points

Silencing miR‐17‐5p leads to significant recovery of neural function in spinal cord injury rats, and downregulation significantly reduces astrocyte activation.
The expression levels of miR‐17‐5p decrease the levels of its target Mfn2, leading to enhanced astrocyte proliferation and inflammatory responses.
Using dual-luciferase reporter assay confirmed Mfn2 as a downstream target gene of miR‐17‐5p, suggesting a regulatory relationship during spinal cord injury.
In vitro activation of astrocytes and quantification of inflammatory cytokines helped to establish the impact of miR‐17‐5p in injury models.

Abstract

ABSTRACT 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.

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