Silencing of SH3BP2 Inhibits Microglia Activation Via the JAK/STAT Signaling in Spinal Cord Injury Models

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 2024 Nov 15

PMID 39546158

Authors

Mingqiong Yu

Fengrui Wang

Ke Han

Affiliations

Soon will be listed here.

Abstract

The purpose of our study was to investigate the expression of SH3 domain-binding protein 2 (SH3BP2) in spinal cord injury (SCI) rats and lipopolysaccharide (LPS)-induced microglia, and explored its impact as well as potential mechanism. We examined the level of SH3BP2 in SCI rats using GEO data, immunofluorescence co-staining, qRT-PCR and western blotting. Next, we constructed a rat model with SH3BP2 silencing by injecting LV-shSH3BP2 into the injury site of SCI rats, and then evaluated its neurological outcome, functional recovery, M1 polarization and neuroinflammation by Basso-Beattie-Bresnahan (BBB) score, inclined plane test, Nissl staining and hematoxylin-eosin (H&E). The SH3BP2-related signaling pathway was predicted by KEGG analysis in GSE45006 dataset. BV2 microglial cells and primary microglia were incubated with LPS, and then measured its activation and inflammation by qRT-PCR, western blotting and immunofluorescence. Further complement experiments were performed to explore the molecular mechanisms of SH3BP2. The expression of SH3BP2 was increased in the spinal dorsal horn tissues of SCI rats and LPS-induced microglia. Silencing of SH3BP2 improved neurological outcomes and functional recovery, attenuated neuroinflammation and microglia polarization in SCI rats. Additionally, the JAK/STAT pathway was regulated by SH3BP2. Silencing of SH3BP2 inhibited LPS-induced microglia inflammation and activation, decreased the phosphorylation levels of JAK and STAT. Silencing of SH3BP2 attenuated SCI by regulating the JAK/STAT pathway to inhibit the activation of microglia.

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