炎症
心肌梗塞
髓系细胞
基因敲除
髓样
下调和上调
单核细胞
化学
癌症研究
细胞生物学
药理学
医学
心脏病学
内科学
生物
细胞凋亡
生物化学
基因
作者
Wenjing Zhou,Qingsong Tang,Shengnan Wang,Ding Liu,Ming Chen,H Liu,Wu Yong,Xin Xiong,Zhenya Shen,Weiqian Chen
标识
DOI:10.1016/j.intimp.2024.111883
摘要
Infarct healing requires a dynamic and orchestrated inflammatory reaction following myocardial infarction (MI). While an uncontrolled excessive inflammatory response exaggerates ischemic injury post-MI, M2-like reparative macrophages may facilitate inflammation regression and promote myocardial healing. However, how protein post-translational modification regulates post-MI cardiac repair and dynamic myeloid activation remains unknown. Here we show that M2-like reparative, but not M1-like inflammatory activation, is enhanced by pharmacologically-induced hyper-O-GlcNAcylation. Mechanistically, myeloid knockdown of O-GlcNAc hydrolase O-GlcNAcase (Oga), which also results in hyper-O-GlcNAcylation, positively regulates M2-like activation in a STAT6-dependent fashion, which is controlled by O-GlcNAcylation of STAT6. Of note, both systemic and local supplementation of thiamet-G (TMG), an Oga inhibitor, effectively facilitates cardiac recovery in mice by elevating the accumulation of M2-like macrophages in infarcted hearts. Our study provides a novel clue for monocyte/macrophage modulating therapies aimed at reducing post-MI hyperinflammation in ischemic myocardium.
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