TREM2 通过 JAK2/STAT3 轴影响糖酵解以中断小胶质细胞 M1 极化和炎症反应

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Chanyuan Liu, Xueying Zhou
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引用次数: 0

摘要

脑缺血/再灌注损伤(IRI)是缺血性脑卒中的主要病理生理基础,缺血性脑卒中是一种严重致残和致死的可怕脑血管事件。髓系细胞上表达的触发受体 2(TREM2)是一种膜糖蛋白,被认为是脑缺血中风的保护因子。在此基础上,本文旨在解释 TREM2 对脑缺血中风的可能活性和下游机制。在氧-葡萄糖剥夺和再灌注(OGD/R)条件下,在小鼠小胶质细胞 BV2 细胞中模拟脑 IRI。Western印迹检测了TREM2和janus kinase 2 (JAK2) /signal transducer and activator of transcription 3 (STAT3)轴相关蛋白的表达。ELISA 和 RT-qPCR 检测了炎症细胞因子的分泌。免疫荧光和 Western 印迹法评估了巨噬细胞的极化情况。通过评估乳酸和细胞外酸化率(ECAR)来衡量糖酵解的激活情况。RT-qPCR和Western印迹检查了糖酵解基因的表达。TREM2 在 BV2 细胞中异常表达,JAK2/STAT3 轴在 OGD/R 反应中异常激活。TREM2 的升高抑制了炎症反应和糖酵解,抑制了 JAK2/STAT3 轴,同时促进了 OGD/R 损伤的 BV2 细胞中 M1 到 M2 的极化。上调的 TREM2 可使糖酵解途径失活,从而缓解 OGD/R 诱导的炎症损伤和 M1 巨噬细胞极化。此外,STAT3激活剂可乐定会加重糖酵解和炎症损伤,并促使暴露于OGD/R的TREM2表达的BV2细胞出现M1样巨噬细胞极化。总之,TREM2可能在脑IRI中产生抗炎潜能,这可能取决于通过JAK2/STAT3轴的中介作用使糖酵解途径失活。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

TREM2 Impairs Glycolysis to Interrupt Microglial M1 Polarization and Inflammation via JAK2/STAT3 Axis.

TREM2 Impairs Glycolysis to Interrupt Microglial M1 Polarization and Inflammation via JAK2/STAT3 Axis.

Cerebral ischemia/reperfusion injury (IRI) is a primary pathophysiological basis of ischemic stroke, a dreadful cerebrovascular event carrying substantial disability and lethality. Triggering receptor expressed on myeloid cells 2 (TREM2) is a membrane glycoprotein that has been notified as a protective factor for cerebral ischemic stroke. On this basis, the paper is thereby goaled to interpret the probable activity and downstream mechanism of TREM2 against cerebral IRI. Cerebral IRI was simulated in murine microglial BV2 cells under oxygen-glucose deprivation and reperfusion (OGD/R) conditions. Western blotting ascertained the expressions of TREM2 and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) axis-associated proteins. ELISA and RT-qPCR assayed the secretion of inflammatory cytokines. Immunofluorescence and western blotting estimated macrophage polarization. Glycolysis activation was measured through evaluating lactic acid and extracellular acidification rate (ECAR). RT-qPCR and western blotting examined the expressions of glycolytic genes. TREM2 was abnormally expressed and JAK2/STAT3 axis was aberrantly activated in BV2 cells in response to OGD/R. Elevation of TREM2 repressed the inflammatory reaction and glycolysis, inhibited the JAK2/STAT3 axis, whereas promoted M1-to-M2 polarization in OGD/R-injured BV2 cells. Upregulated TREM2 inactivated the glycolytic pathway to relieve OGD/R-induced inflammatory injury and M1 macrophage polarization. Besides, STAT3 activator, colivelin, aggravated the glycolysis, inflammatory injury and drove M1-like macrophage polarization in TREM2-overexpressing BV2 cells exposed to OGD/R. Collectively, TREM2 might produce anti-inflammatory potential in cerebral IRI, which might dependent on the inactivation of glycolytic pathway via intermediating the JAK2/STAT3 axis.

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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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