Nrf2 Inhibits GAPDH/Siah1 Axis to Reduce Inflammatory Reactions and Proliferation of Microglia After Simulating Spinal Cord Injury

Chunhe Sha; Feng Pan; Zhiqing Wang; Guohui Liu; Hua Wang; Tianwei Huang; Kai Huang

doi:10.2174/0115665240280178231218093609

Nrf2 Inhibits GAPDH/Siah1 Axis to Reduce Inflammatory Reactions and Proliferation of Microglia After Simulating Spinal Cord Injury

Curr Mol Med. 2024 Jan 10. doi: 10.2174/0115665240280178231218093609. Online ahead of print.

Authors

Chunhe Sha¹, Feng Pan¹, Zhiqing Wang¹, Guohui Liu¹, Hua Wang¹, Tianwei Huang¹, Kai Huang¹

Affiliation

¹ Department of Orthopaedics, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, 200070, China.

PMID: 38213136
DOI: 10.2174/0115665240280178231218093609

Abstract

Objective: To explore the effect of nuclear factor erythroid 2-related factor 2 (Nrf 2) on microglial inflammatory response and proliferation after spinal cord injury (SCI) through the glyceraldehyde phosphate dehydrogenase (GAPDH) / Seven in absentia homolog 1 (Siah 1) signaling pathway.

Methods: Human microglia HMC3 was induced by lipopolysaccharide (LPS) to establish a SCI cell model. Microglia morphology after LPS stimulation was observed by transmission electron microscope (TEM), and cellular Nrf2, GAPDH/Siah1 pathway expression and cell viability were determined. Subsequently, the Nrf2 overexpression plasmid was transfected into microglia to observe changes in cell viability and GAPDH/Siah1 pathway expression.

Results: Microglia, mostly amoeba-like, were found to have enlarged cell bodies after LPS stimulation, with an increased number of cell branches, highly expressed Nrf2, GAPDH and Siah1, and decreased cell viability (P<0.05). Up-regulating Nrf2 inhibited the GAPDH/Siah1 axis, decreased inflammatory responses, and enhanced activity in post-SCI microglia (P<0.05).

Conclusion: Up-regulating Nrf2 expression can reverse the inflammatory reaction of microglia after LPS stimulation and enhance their activity by inhibiting the GAPDH/Siah1 axis.

Keywords: Nrf2 inhibits GAPDH/Siah1 signaling pathways; inflammatory reactions.; microglia; spinal cord injury.