Zhang Fuan, Han Chong, Chen Jiao, Chen Ziqiang, Ding Ning, Zhang Xuyang, Zhao Fengchun, Zhang Lanying, Wang Peirui, Cao Fang, Hu Rong, Yao Shengtao
Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Zunyi, Guizhou, 563000, China.
Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Zunyi, Guizhou, 563000, China.
Life Sci. 2025 Dec 1;382:124023. doi: 10.1016/j.lfs.2025.124023. Epub 2025 Oct 14.
The effect of miR-146b-5p on microglial polarization and neuroinflammation post-intracerebral hemorrhage (ICH) remains unclear. We investigated the role of circulating plasma exosomal miR-146b-5p in microglial polarization and neuroinflammation following ICH.
Plasma was isolated from peripheral blood collected from ICH patients and healthy individuals. Bioinformatic analysis identified differentially expressed miRNAs and their target genes. The interaction between miR-146b-5p and its target genes was confirmed using a dual-luciferase reporter assay. Using lipopolysaccharide (LPS)-induced microglial inflammation and ICH mouse models, we assessed the role of miR-146b-5p in microglial polarization and neuroinflammation. miR-146b-5p's regulatory influence on the tumor necrosis factor receptor-associated factor 6/nuclear factor kappa B (TRAF6/NF-κB) pathway was confirmed using knockdown and overexpression experiments of TRAF6.
The plasma exosome levels of miR-146b-5p in ICH were markedly reduced compared to those in healthy controls. miR-146b-5p overexpression facilitated M2 polarization of microglia and decreased TNF-α, interleukin-1β (IL-1β), and IL-6 levels. Conversely, inhibition of miR-146b-5p had the opposite effect. A dual-luciferase assay indicated that TRAF6 was directly targeted by miR-146b-5p. TRAF6 knockdown inhibited NF-κB activation and enhanced M2 polarization. However, TRAF6 overexpression reversed these effects. Rescue experiments demonstrated that TRAF6 knockdown reversed the phenotypic effects of the miR-146b-5p inhibitor.
Circulating plasma exosomal miR-146b-5p modulates microglial polarization and neuroinflammation via the TRAF6/NF-κB signaling pathway following ICH, providing neuroprotective benefits. These findings may contribute to the development of innovative therapeutic approaches.
