Liu Chanyuan, Zhou Xueying
Psychiatric Ward 1, Wuhan Wuchang Hospital, Wuhan, 430061, Hubei, China.
Department of Psychiatry, Liyuan Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430077, Hubei, China.
Cell Biochem Biophys. 2025 Mar;83(1):879-891. doi: 10.1007/s12013-024-01520-5. Epub 2024 Sep 6.
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.
脑缺血/再灌注损伤（IRI）是缺血性中风的主要病理生理基础，缺血性中风是一种可怕的脑血管事件，具有严重的致残率和致死率。髓系细胞触发受体2（TREM2）是一种膜糖蛋白，已被确认为脑缺血性中风的保护因子。在此基础上，本文旨在阐释TREM2抗脑IRI的可能活性及下游机制。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中模拟脑IRI。蛋白质印迹法确定TREM2和janus激酶2（JAK2）/信号转导子和转录激活子3（STAT3）轴相关蛋白的表达。酶联免疫吸附测定法（ELISA）和逆转录-定量聚合酶链反应（RT-qPCR）检测炎性细胞因子的分泌。免疫荧光和蛋白质印迹法评估巨噬细胞极化。通过评估乳酸和细胞外酸化率（ECAR）来测定糖酵解激活。RT-qPCR和蛋白质印迹法检测糖酵解基因的表达。在响应OGD/R时，BV2细胞中TREM2异常表达，JAK2/STAT3轴异常激活。TREM2的升高抑制了炎症反应和糖酵解，抑制了JAK2/STAT3轴，而在OGD/R损伤的BV2细胞中促进了M1向M2极化。上调的TREM2使糖酵解途径失活，以减轻OGD/R诱导的炎症损伤和M1巨噬细胞极化。此外，STAT3激活剂colivelin加剧了糖酵解、炎症损伤，并在暴露于OGD/R的TREM2过表达BV2细胞中驱动M1样巨噬细胞极化。总的来说，TREM2可能在脑IRI中产生抗炎潜力，这可能依赖于通过介导JAK2/STAT3轴使糖酵解途径失活。
