巨噬细胞极化
再灌注损伤
泛素连接酶
炎症
缺血
细胞生物学
免疫学
信号转导
生物
巨噬细胞
泛素
医学
癌症研究
内科学
体外
生物化学
基因
作者
Hao Chen,Yuxing Hou,Yali Zhai,Jie Yang,Linli Que,Jichun Liu,Linming Lu,Tuanzhu Ha,Chuanfu Li,Yong Xu,Jiantao Li,Yuehua Li
标识
DOI:10.1093/jleuko/qiac012
摘要
The polarization of macrophages to the M1 or M2 phenotype has a pivotal role in inflammatory response following myocardial ischemia/reperfusion injury. Peli1, an E3 ubiquitin ligase, is closely associated with inflammation and autoimmunity as an important regulatory protein in the Toll-like receptor signaling pathway. We aimed to explore the function of Peli1 in macrophage polarization under myocardial ischemia/reperfusion injury and elucidate the possible mechanisms. We show here that Peli1 is upregulated in peripheral blood mononuclear cells from patients with myocardial ischemia/reperfusion, which is correlated with myocardial injury and cardiac dysfunction. We also found that the proportion of M1 macrophages was reduced and myocardial infarct size was decreased, paralleling improvement of cardiac function in mice with Peli1 deletion in hematopoietic cells or macrophages. Macrophage Peli1 deletion lessened M1 polarization and reduced the migratory ability in vitro. Mechanistically, Peli1 contributed to M1 polarization by promoting K63-linked ubiquitination and nuclear translocation of IRF5. Moreover, Peli1 deficiency in macrophages reduced the apoptosis of cardiomyocytes in vivo and in vitro. Together, our study demonstrates that Peli1 deficiency in macrophages suppresses macrophage M1 polarization and alleviates myocardial ischemia/reperfusion injury by inhibiting the nuclear translocation of IRF5, which may serve as a potential intervention target for myocardial ischemia/reperfusion injury.
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