Title:Nrf2 Inhibits GAPDH/Siah1 Axis to Reduce Inflammatory Reactions and Proliferation of Microglia After Simulating Spinal Cord Injury
Volume: 24
Author(s): Chunhe Sha, Feng Pan, Zhiqing Wang, Guohui Liu, Hua Wang, Tianwei Huang and Kai Huang*
Affiliation:
- Department of Orthopaedics, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, 200070, China
Keywords:
Nrf2 inhibits GAPDH/Siah1 signaling pathways, spinal cord injury, microglia, inflammatory reactions.
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.
