髓系细胞触发受体2在高糖处理的小胶质细胞中的表达及作用

doi:10.16352/j.issn.1001-6325.2024.02.0167

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (2): 167-173.doi: 10.16352/j.issn.1001-6325.2024.02.0167

髓系细胞触发受体2在高糖处理的小胶质细胞中的表达及作用

王曌慧¹, 刘潇¹, 周玥¹, 魏心怡¹, 王玥^2,3, 李俊发¹, 赵丽^1*

1.首都医科大学基础医学院神经生物学系,北京 100006;
2.首都医科大学附属北京安定医院国家精神心理疾病临床医学研究中心精神疾病诊断与治疗北京市重点实验室,北京 100088;
3.首都医科大学人脑保护高精尖创新中心,北京 100069

收稿日期:2023-11-01 修回日期:2023-12-26 发布日期:2024-02-05
通讯作者: ^*zhaoli@ccmu.edu.cn
基金资助:
国家自然科学基金(82071539);北京市自然科学基金(7232003,7222064)

Expression and role of triggering receptor expressed on myeloid cells 2 in high glucose-treated microglia

WANG Zhaohui¹, LIU Xiao¹, ZHOU Yue¹, WEI Xinyi¹, WANG Yue^2,3, LI Junfa¹, ZHAO Li^1*

1. Department of Neurobiology, School of Basic Medicine, Capital Medical University, Beijing 100006;
2. Beijing Key Laboratory of Diagnosis and Treatment of Mental Disorders, National Clinical Medical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088;
3. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China

Received:2023-11-01 Revised:2023-12-26 Published:2024-02-05
Contact: ^*zhaoli@ccmu.edu.cn

摘要/Abstract

摘要： 目的探索高糖条件下小胶质细胞中髓系细胞触发受体2(triggering receptor expressed on myeloid cells 2, TREM2)的表达情况,以及TREM2在高糖条件下小胶质细胞增殖、迁移和吞噬中的作用。方法小胶质细胞分为对照组、高糖处理组(67.5 mmol/L葡萄糖,24 h),检测小胶质细胞数量、Iba1和TREM2的表达水平;转染TREM2的siRNA,检测小胶质细胞增殖和迁移能力的变化;加入带有荧光标签的淀粉样蛋白β(Aβ),观察小胶质细胞对Aβ吞噬能力的影响。结果与正常小胶质细胞相比,高糖处理后小胶质细胞的数量明显下降(P＜0.001),而TREM2和Iba1表达显著升高(P＜0.001)。高糖和TREM2均不影响小胶质细胞的增殖能力。与正常组相比,高糖处理后小胶质细胞迁移能力下降(P＜0.05),而TREM2对高糖小胶质细胞的迁移能力无显著影响。与正常小胶质细胞相比,高糖处理组小胶质细胞对Aβ的吞噬能力显著下降(P＜0.001),TREM2 siRNA敲减后高糖小胶质细胞对Aβ的吞噬能力进一步下降(P＜0.001)。结论高糖处理后小胶质细胞TREM2表达明显升高,其主要影响小胶质细胞对Aβ的吞噬能力。

关键词: 高糖, 小胶质细胞, 髓系细胞触发受体2

Abstract: Objective To explore the expression of triggering receptor expressed on myeloid cells 2 (TREM2) in high-glucose microglia and to investigate the role of TREM2 in the proliferation, migration and phagocytosis of high-glucose microglia. Methods Microglia cells were divided into control group and high-glucose treatment group(67.5 mmol/L glucose, 24 h). The microglia cells were counted and the expression of Iba1 and TREM2 was detected. TREM2 siRNA was transfected to detect the proliferation and migration of microglia. The amyloid β-peptide (Aβ) with a fluorescent tag was added to observe the phagocytosis of Aβ by microglia. Results Compared to normal microglia, the number of microglia significantly decreased after high-glucose treatment (P＜0.001), while the expression of TREM2 and Iba1 markedly increased (P＜0.001). High glucose and TREM2 did not affect the proliferation of microglia. Compared to the normal group, the migration of microglia significantly decreased after high-glucose treatment (P＜0.05) and TREM2 did not affect the migration ability of high-glucose microglia. Compared to the normal group, the phagocytosis of Aβ by microglia significantly decreased in the high-glucose treated group(P＜0.001). Furthermore, TREM2 knockdown further decreased the phagocytosis of Aβ by high-glucose microglia (P＜0.001). Conclusions The expression of TREM2 in microglia significantly increases after high-glucose treatment, which significantly affects phagocytosis of Aβ by microglia.

Key words: high glucose, microglia, myeloid cell trigger receptor 2 (TREM2)

中图分类号:

R587.1

王曌慧, 刘潇, 周玥, 魏心怡, 王玥, 李俊发, 赵丽. 髓系细胞触发受体2在高糖处理的小胶质细胞中的表达及作用[J]. 基础医学与临床, 2024, 44(2): 167-173.

WANG Zhaohui, LIU Xiao, ZHOU Yue, WEI Xinyi, WANG Yue, LI Junfa, ZHAO Li. Expression and role of triggering receptor expressed on myeloid cells 2 in high glucose-treated microglia[J]. Basic & Clinical Medicine, 2024, 44(2): 167-173.

参考文献

[1]Ennis GE, Saelzler U, Umpierrez GE, et al. Prediabetes and working memory in older adults[J].Brain Neurosci Adv, 2020, 4:239821282096172. doi: 10.1177/2398212820961725.
[2]Cui Y, Yang M, Wang Y, et al. Melatonin prevents diabetes-associated cognitive dysfunction from microglia-mediated neuroinflammation by activating autophagy via TLR4/Akt/mTOR pathway[J]. FASEB J, 2021, 35: e21485. doi: 10.1096/fj.202002247RR.
[3]Pickering J , Wong R, Al-Salami H,et al. Cognitive deficits in type-1 diabetes: aspects of glucose, cerebrovascular and amyloid involvement.[J]. PHARM RES-DORDR, 2021, 38:1477-1484. doi: 10.1007/s11095-021-03100-1.
[4]Keren-Shaul H, Spinrad A, Weiner A,et al. A unique microglia type associated with restricting development of Alzheimer's disease.[J].Cell, 2017; 169:1276-1290. doi: 10.1016/j.cell.2017.05.018.
[5]La Rosa F, Agostini S, Piancone F, et al. TREM2 expression and amyloid-beta phagocytosis in Alzheimer's disease[J] Int J Mol Sci. 2023;24:8626. doi: 10.3390/ijms24108626.
[6]Cignarella F, Filipello F, Bollman B,et al. TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis[J].Acta Neuropath, 2020, 140:513-534. doi: 10.1007/s00401-020-02193-z.
[7]Jericó I, Vicuña-Urriza J, Blanco-Luquin I, et al. Profil-ing TREM2 expression in amyotrophic lateral sclerosis[J] Brain Behav Immun. 2023,109:117-126. doi: 10.1016/j.bbi.2023.01.013.
[8]Zhu Y, Guo L, Zou J, et al. JQ1 inhibits high glucose-induced migration of retinal microglial cells by regulating the PI3K/AKT signaling pathway[J] Math Biosci Eng. 2022,19:13079-13092. doi: 10.3934/mbe.2022611.
[9]Hierro-Bujalance C, Del Marco A, José Ramos-Rodríguez J, et al. Cell proliferation and neurogenesis alterations in Alzheimer's disease and diabetes mellitus mixed murine models[J]. J Neurochem. 2020, 154:673-692. doi: 10.1111/jnc.14987.
[10]Liu H, Bian W, Yang D, et al. Inhibiting the Piezo1 channel protects microglia from acute hypergly-caemia damage through the JNK1 and mTOR signalling pathways[J].Life Sci, 2021, 264:118667. doi: 10.1016/j.lfs.2020.118667.
[11]Sciaccaluga M, Megaro A, Bellomo G, et al. An unbalanced synaptic transmission: cause or consequence of the amyloid oligomers neurotoxicity[J] Int J Mol Sci. 2021,22:5991. doi: 10.3390/ijms22115991.
[12]Yeh F, Wang Y, Tom I,et al. TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-beta by microglia[J].Neuron, 2016, 91:328-340. doi: 10.1016/j.neuron.
[13]Claes C, Van Den Daele J, Boon R, et al. Human stem cell-derived monocytes and microglia-like cells reveal impaired amyloid plaque clearance upon heterozygous or homozygous loss of TREM2[J] Alzheimers Dement, 2019,15:453-464. doi: 10.1016/j.jalz.2018.09.006.
[14]Lee CYD, Daggett A, Gu X,et al. Elevated TREM2 gene dosage reprograms microglia responsivity and ameliorates pathological phenotypes in Alzheimer's disease models[J].Neuron, 2018, 97:1032. doi: 10.1016/j.neuron.2018.02.002.

[1]	朱锋, 钟粤, 邓义江, 刘文值, 边疆. 右美托咪定通过上调PPAR-γ改善神经病理性疼痛模型大鼠的痛觉敏化[J]. 基础医学与临床, 2023, 43(9): 1369-1374.
[2]	许津铭, 洪语萱, 韦晖, 许琪. 抗SARS-CoV-2相关线性表位抗体诱发小鼠神经炎性反应[J]. 基础医学与临床, 2023, 43(3): 438-443.
[3]	张梦瑶, 牛姝, 蔡静, 张立香, 赵志刚. 丹参酮ⅡA减轻高糖诱导的小鼠足细胞系PMC-5凋亡和氧化应激反应[J]. 基础医学与临床, 2023, 43(2): 277-282.
[4]	张凤云, 赵志浩, 张卓琦. miR-34a对高糖状态下小鼠巨噬细胞系RAW264.7极化及炎性因子分泌的影响[J]. 基础医学与临床, 2023, 43(12): 1808-1813.
[5]	郑建滨, 吴少华, 黄玉景. IL-6促进小鼠小胶质细胞系BV2坏死性凋亡[J]. 基础医学与临床, 2023, 43(10): 1562-1566.
[6]	王远卓, 郑清月, 张翰林, 仇文颖, 王涛, 马超. 小胶质细胞在阿尔茨海默病神经炎性反应中作用的研究进展[J]. 基础医学与临床, 2022, 42(8): 1310-1313.
[7]	陈宁宁, 应新旺, 谢庆凤. 抑制小凹蛋白减轻大鼠脑缺血/再灌注诱导的神经功能损伤[J]. 基础医学与临床, 2022, 42(12): 1879-1884.
[8]	秦建民, 张来香, 魏振英. miR-193a-3p抑制高糖诱导人视网膜血管内皮细胞凋亡[J]. 基础医学与临床, 2021, 41(7): 995-1000.
[9]	林敏, 张红梅. 白藜芦醇通过上调annexin A1表达促进氧糖剥夺/复氧大鼠小胶质细胞系向M2型极化[J]. 基础医学与临床, 2021, 41(5): 715-720.
[10]	李辰, 修建波, 许琪. PARP14在3种抑郁症模型小鼠海马区的表达升高及其与神经炎性反应的关系[J]. 基础医学与临床, 2021, 41(5): 641-647.
[11]	王紫涵, 罗金定, 田英入, 奉水东, 凌宏艳. 小胶质细胞引起和促进阿尔茨海默病的研究进展[J]. 基础医学与临床, 2021, 41(2): 277-281.
[12]	曲野, 刘立柱, 徐瑞敏, 吴开弟, 代伟宏. miR-295抑制高糖诱导的小鼠成骨细胞系MC3T3-E1的凋亡[J]. 基础医学与临床, 2021, 41(11): 1588-1593.
[13]	孙凤起, 武韧, 常贵全, 李鸿珠. 肾小球系膜细胞增殖在糖尿病肾病肾小球硬化中作用的研究进展[J]. 基础医学与临床, 2021, 41(10): 1510-1513.
[14]	周丽萍, 毛晓春, 李琴. miR-1908抑制高糖诱导的人视网膜血管内皮细胞系HRECs凋亡[J]. 基础医学与临床, 2020, 40(8): 1090-1095.
[15]	刘雯霞, 刘彩红, 郭蕊, 孟芝君, 高佳, 王亚静. 尼古丁促进高糖/高脂培养的大鼠心肌细胞系H9C2凋亡[J]. 基础医学与临床, 2020, 40(1): 24-29.

髓系细胞触发受体2在高糖处理的小胶质细胞中的表达及作用

Expression and role of triggering receptor expressed on myeloid cells 2 in high glucose-treated microglia

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价