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

IF 2.2 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current molecular medicine Pub Date : 2024-01-10 DOI:10.2174/0115665240280178231218093609

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

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引用次数: 0

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.

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Nrf2抑制GAPDH/Siah1轴以减少模拟脊髓损伤后的炎症反应和小胶质细胞增殖

目的方法：用脂多糖（LPS）诱导人小胶质细胞HMC3，建立脊髓损伤（SCI）细胞模型。透射电子显微镜（TEM）观察了LPS刺激后的小胶质细胞形态，并测定了细胞Nrf2、GAPDH/Siah1通路的表达和细胞活力。随后，将 Nrf2 过表达质粒转染到小胶质细胞中，观察细胞活力和 GAPDH/Siah1 通路表达的变化：结果：发现小胶质细胞在LPS刺激后细胞体增大，细胞分支增多，Nrf2、GAPDH和Siah1高表达，细胞活力下降（PConclusion：上调 Nrf2 的表达可逆转小胶质细胞在 LPS 刺激后的炎症反应，并通过抑制 GAPDH/Siah1 轴增强其活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular medicine 医学-医学：研究与实验

CiteScore

5.00

自引率

4.00%

发文量

141

审稿时长

4-8 weeks

期刊介绍： Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.