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

doi:10.16352/j.issn.1001-6325.2025.10.1341

Abstract

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

CLC Number:

R543.5

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.

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