当前位置: X-MOL 学术Basic Res. Cardiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
HIMF deletion ameliorates acute myocardial ischemic injury by promoting macrophage transformation to reparative subtype
Basic Research in Cardiology ( IF 9.5 ) Pub Date : 2021-04-23 , DOI: 10.1007/s00395-021-00867-7
Yanjiao Li 1, 2 , Min Dong 1, 2 , Qing Wang 1, 2 , Santosh Kumar 1, 2 , Rui Zhang 1, 2 , Wanwen Cheng 1, 2 , Jiaqing Xiang 1, 2 , Gang Wang 1, 2 , Kunfu Ouyang 3 , Ruxing Zhou 1, 2 , Yaohong Xie 1, 2 , Yishen Lu 1, 2 , Jing Yi 1, 2 , Haixia Duan 1, 2 , Jie Liu 1, 2
Affiliation  

Appropriately manipulating macrophage M1/M2 phenotypic transition is a promising therapeutic strategy for tissue repair after myocardial infarction (MI). Here we showed that gene ablation of hypoxia-induced mitogenic factor (HIMF) in mice (Himf−/− and HIMFflox/flox;Lyz2-Cre) attenuated M1 macrophage-dominated inflammatory response and promoted M2 macrophage accumulation in infarcted hearts. This in turn reduced myocardial infarct size and improved cardiac function after MI. Correspondingly, expression of HIMF in macrophages induced expression of pro-inflammatory cytokines; the culturing medium of HIMF-overexpressing macrophages impaired the cardiac fibroblast viability and function. Furthermore, macrophage HIMF was found to up-regulate C/EBP-homologous protein (CHOP) expression, which exaggerated the release of pro-inflammatory cytokines via activating signal transducer of activator of transcription 1 (STAT1) and 3 (STAT3) signaling. Together these data suggested that HIMF promotes M1-type and prohibits M2-type macrophage polarization by activating the CHOP–STAT1/STAT3 signaling pathway to negatively regulate myocardial repair. HIMF might thus constitute a novel target to treat MI.



中文翻译:

HIMF缺失通过促进巨噬细胞转化为修复亚型来改善急性心肌缺血性损伤

适当地操纵巨噬细胞 M1/M2 表型转变是心肌梗死 (MI) 后组织修复的一种有前途的治疗策略。在这里,我们展示了小鼠缺氧诱导有丝分裂因子 (HIMF) 的基因消融(Himf -/-和 HIMF flox/flox;Lyz2-Cre) 减弱 M1 巨噬细胞主导的炎症反应并促进 M2 巨噬细胞在梗塞心脏中的积累。这反过来又减少了心肌梗死面积并改善了 MI 后的心脏功能。相应地,巨噬细胞中 HIMF 的表达诱导促炎细胞因子的表达;过表达 HIMF 的巨噬细胞的培养基会损害心脏成纤维细胞的活力和功能。此外,发现巨噬细胞 HIMF 上调 C/EBP 同源蛋白 (CHOP) 表达,这通过激活转录激活因子 1 (STAT1) 和 3 (STAT3) 信号传导的信号转导夸大了促炎细胞因子的释放。这些数据共同表明,HIMF 通过激活 CHOP-STAT1/STAT3 信号通路负调节心肌修复,促进 M1 型和抑制 M2 型巨噬细胞极化。因此,HIMF 可能构成治疗 MI 的新靶点。

更新日期:2021-04-23
down
wechat
bug