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Published on: November 23, 2014
Silencing of SH3BP2 Inhibits Microglia Activation Via the JAK/STAT Signaling in Spinal Cord Injury Models
Mingqiong Yu1, Fengrui Wang2, Ke Han3
1Department of Tuina, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
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.
Insights
SH3 domain-binding protein 2 (SH3BP2) is upregulated in spinal cord injury (SCI) and microglia. Silencing SH3BP2 improves recovery by inhibiting neuroinflammation and microglia activation via the JAK/STAT pathway.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Spinal cord injury (SCI) triggers significant neuroinflammation and microglial activation.
- SH3 domain-binding protein 2 (SH3BP2) is implicated in cellular signaling pathways relevant to injury responses.
Purpose of the Study:
- To investigate SH3BP2 expression in SCI rat models and lipopolysaccharide (LPS)-induced microglia.
- To explore the impact and underlying mechanisms of SH3BP2 in SCI and neuroinflammation.
Main Methods:
- Analysis of GEO data, immunofluorescence, qRT-PCR, and western blotting in SCI rats.
- SH3BP2 silencing in SCI rats and LPS-treated microglia models.
- Assessment of neurological outcomes, functional recovery, microglial polarization, and inflammatory markers.
- KEGG pathway analysis and JAK/STAT pathway investigation.
Main Results:
- SH3BP2 expression was elevated in SCI spinal cord tissues and LPS-induced microglia.
- SH3BP2 silencing improved neurological function, reduced neuroinflammation, and attenuated M1 microglial polarization in SCI rats.
- SH3BP2 silencing inhibited LPS-induced microglia activation and inflammation by downregulating JAK/STAT pathway phosphorylation.
Conclusions:
- SH3BP2 plays a critical role in SCI pathogenesis and neuroinflammation.
- Targeting SH3BP2, potentially through the JAK/STAT pathway, offers a therapeutic strategy for SCI.
- SH3BP2 inhibition attenuates SCI by suppressing microglia activation and neuroinflammation.
