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

## TL;DR

This study shows that increasing Nrf2 reduces inflammation and boosts activity in microglia cells after spinal cord injury by blocking the GAPDH/Siah1 pathway.

## Contribution

The novel finding is that Nrf2 inhibits the GAPDH/Siah1 axis to reduce microglial inflammation and proliferation after spinal cord injury.

## Key findings

- Up-regulating Nrf2 inhibited the GAPDH/Siah1 axis in microglia.
- Nrf2 overexpression decreased inflammatory responses and enhanced cell viability after LPS stimulation.
- LPS-stimulated microglia showed increased Nrf2, GAPDH, and Siah1 expression with reduced viability.

## Abstract

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.

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.

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).

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