下调METTL3降低Hcy诱导的巨噬细胞M1极化和泡沫化

doi:10.16352/j.issn.1001-6325.2025.10.1341

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (10): 1341-1349.doi: 10.16352/j.issn.1001-6325.2025.10.1341

下调METTL3降低Hcy诱导的巨噬细胞M1极化和泡沫化

梁宇, 李俊虹, 王建琼, 魏丽, 蒋杰, 王明圆, 苏敏^*

云南省第一人民医院/昆明理工大学附属医院检验科,云南昆明 650034

收稿日期:2024-10-29 修回日期:2024-12-31 出版日期:2025-10-05 发布日期:2025-09-22
通讯作者: ^*nxykdxjyxy@163.com
基金资助:
昆明医科大学联合基金面上项目(202301AY070001-144); 云南省基础研究面上项目(202301AT070033); 云南省第一人民医院高层次人才引进补助项目(2022-KHRCBZ-B02)

Down-regulation of METTL3 reduces Hcy-induced macrophage M1 polarization and foaminess

LIANG Yu, LI Junhong, WANG Jianqiong, WEI Li, JIANG Jie, WANG Mingyuan, SU Min^*

Department of Clinical Laboratory, the First People's Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming 650034, China

Received:2024-10-29 Revised:2024-12-31 Online:2025-10-05 Published:2025-09-22
Contact: ^*nxykdxjyxy@163.com

摘要/Abstract

摘要： 目的探究同型半胱氨酸(Hcy)对巨噬细胞极化和泡沫化的调节作用及潜在作用机制。方法应用酶联免疫吸附试验(ELISA)和流式细胞术检测Hcy处理对巨噬细胞极化的调节作用;试剂盒检测胞内各种形式的胆固醇的含量以及应用油红O染色和Dil标记的氧化低密度脂蛋白(Dil-oxLDL)评估Hcy对胞内脂质积累和ox-LDL摄取的影响;荧光定量PCR(qRT-PCR)和Western blot检测N6-甲基腺苷(m⁶A)修饰关键基因的mRNA和蛋白表达。结果 Hcy促进巨噬细胞和ox-LDL诱导的泡沫巨噬细胞向M1极化,并且促进细胞对ox-LDL的摄取和胞内脂质积累。此外,Hcy能够上调甲基转移酶样蛋白3(METTL3)的表达。抑制或敲低METTL3的表达后,Hcy对促进巨噬细胞M1极化和泡沫化的趋势被明显降低。结论 Hcy可显著促进巨噬细胞M1极化和泡沫化,该作用可能被METTL3的沉默减弱。

关键词: 同型半胱氨酸, 巨噬细胞极化, 巨噬细胞泡沫化, 甲基转移酶样蛋白3, N6-甲基腺苷

Abstract: Objective To investigate the regulation of macrophage polarization and foaminess by homocysteine (Hcy) and its potential underlying mechanisms. Methods ELISA and flow cytometry were used to detect the effect of Hcy treatment on the polarization of macrophages. The contents of various forms of intracellular cholesterol were detected, and the effects of Hcy on intracellular lipid accumulation and ox-LDL uptake were evaluated by oil red O staining and Dil-oxLDL. RT-qPCR and Western blot were used to detect mRNA and protein expression of key genes modified by N6-methyladenosine(m⁶A). Results Hcy promoted M1 polarization of macrophages and ox-LDL-induced foam macrophages and promoted ox-LDL uptake as well as intracellular lipid accumulation. In addition, Hcy upregulated methyltransferase like 3 (METTL3) expression, and the tendency of Hcy to promote macrophage M1 polarization and foaminess was markedly reduced after inhibition or knockdown of METTL3 expression. Conclusions Hcy significantly promotes macrophage M1 polarization and foaminess, an effectthat may be attenuated by METTL3 silencing.

Key words: homocysteine, macrophage polarization, macrophage foam, METTL3, N6-methyladenosine

中图分类号:

R543.5

梁宇, 李俊虹, 王建琼, 魏丽, 蒋杰, 王明圆, 苏敏. 下调METTL3降低Hcy诱导的巨噬细胞M1极化和泡沫化[J]. 基础医学与临床, 2025, 45(10): 1341-1349.

LIANG Yu, LI Junhong, WANG Jianqiong, WEI Li, JIANG Jie, WANG Mingyuan, SU Min. Down-regulation of METTL3 reduces Hcy-induced macrophage M1 polarization and foaminess[J]. Basic & Clinical Medicine, 2025, 45(10): 1341-1349.

参考文献

[1] Blagov AV, Markin AM. The role of macrophages in the pathogenesis of atherosclerosis[J]. Cells, 2023, 12:522. doi: 10.3390/cells12040522.
[2] Wu J, He S, Song Z, et al. Macrophage polarization states in atherosclerosis[J]. Front Immunol, 2023, 14: 1185587. doi: 10.3389/fimmu.2023.1185587.
[3] Zhong X, He R, You S, et al. The roles of aerobic exercise and folate supplementation in hyperhomocysteinemia-accelerated atherosclerosis[J]. Acta Cardiol Sin, 2023, 39: 309-318.
[4] Winchester LJ, Veeranki S, Givvimani S, et al. Homocysteine elicits an M1 phenotype in murine macrophages through an EMMPRIN-mediated pathway[J]. Can J Physiol Pharmacol, 2015, 93: 577-584.
[5] Griñán R, Escolà-Gil JC. Epigenetic regulation by microRNAs in hyperhomocysteinemia-accelerated atherosclerosis[J]. Int J Mol Sci, 2022, 23. doi: 10.3390/ijms232012452.
[6] Guo W, Zhang H, Yang A, et al. Homocysteine accelerates atherosclerosis by inhibiting scavenger receptor class B member1 via DNMT3b/SP1 pathway[J]. J Mol Cell Cardiol, 2020, 138: 34-48.
[7] Hou P, Fang J, Liu Z, et al. Macrophage polarization and metabolism in atherosclerosis[J]. Cell Death Dis,2023, 14: 691. doi: 10.1038/s41419-023-06206-z.
[8] 王文琳, 罗烨, 柯晓. 辣椒来源外泌体样纳米囊泡通过ERK1/2通路拮抗巨噬细胞向泡沫细胞转化[J]. 中国动脉硬化杂志, 2024, 32: 503-513.
[9] Luo M, Zhao F, Cheng H, et al. Macrophage polariza-tion: an important role in inflammatory diseases[J]. Front Immunol, 2024, 15: 1352946. doi: 10.3389/fimmu.2024.1352946.
[10] Gianopoulos I, Daskalopoulou SS. Macrophage profiling in atherosclerosis: understanding the unstable plaque[J]. Basic Res Cardiol,2024, 119: 35-56.
[11] 张鹏举, 李杰, 张梦迪, 等. KAT8通过增强METTL3表达促进结直肠癌细胞系增殖[J]. 基础医学与临床, 2024, 44: 931-939.
[12] Gou Y, Wang H, Wang T, et al. Ectopic endometriotic stromal cells-derived lactate induces M2 macrophage polarization via Mettl3/Trib1/ERK/STAT3 signalling pathway in endometriosis[J]. Immunology,2023, 168: 389-402.
[13] Shu B, Zhou YX, Li H, et al. The METTL3/MALAT1/PTBP1/USP8/TAK1 axis promotes pyroptosis and M1 polarization of macrophages and contributes to liver fibrosis[J]. Cell Death Discov, 2021, 7: 368. doi: 10.1038/s41420-021-00756-x.

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下调METTL3降低Hcy诱导的巨噬细胞M1极化和泡沫化

Down-regulation of METTL3 reduces Hcy-induced macrophage M1 polarization and foaminess

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