Epigenetic mechanism of miR-26b-5p-enriched MSCs-EVs attenuates spinal cord injury

Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising therapies for the treatment of spinal cord injury (SCI). This study sought to explore the epigenetic mechanism of miR-26b-5penriched MSCs-EVs in SCI. MSCs and MSCs-EVs were isolated and characterized. The SCI rat model was established, followed by Basso-Beattie-Bresnahan scoring and H&E staining. In vitro cell models were established in PC12 cells with lipopolysaccharide (LPS) treatment, followed by cell viability evaluation using CCK-8 assay. The levels of miR-26b-5p, lysine demethylase 6A (KDM6A), NADPH oxidase 4 (NOX4), reactive oxygen species (ROS), and inflammatory factors (TNF-a/IL-1b/IL-6) in tissues and cells were detected. The levels of cy3-lablled miR-26b-5p in tissues and cells were observed by confocal microscopy. The binding of miR-26b-5p to KDM6A 30UTR and the enrichments of KDM6A and H3K27me3 at the NOX4 promoter were analyzed. MSCs-EVs attenuated motor dysfunction, inflammation, and oxidative stress in SCI rats. MSCs-EVs delivered miR-26b-5p into PC12 cells to reduce LPS-induced inflammation and ROS production and enhance cell viability. miR-26b-5p inhibited KDM6A, and KDM6A reduced H3K27me3 at the NOX4 promoter to promote NOX4. Overexpression of KDM6A or NOX4 reversed the alleviative role of MSCs-EVs in SCI or LPS-induced cell injury. Overall, MSCs-EVs delivered miR-26b-5p into cells to target the KDM6A/NOX4 axis and facilitate the recovery from SCI. (c) 2023, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Automated summary

This study discovers that MSCs-EVs attenuate inflammation and oxidative stress in spinal cord injury (SCI) by delivering miR-26b-5p to target the KDM6A/NOX4 axis, facilitating recovery.