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

doi:10.16352/j.issn.1001-6325.2024.02.0167

Abstract

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)

CLC Number:

R587.1

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.

References

[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.

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