BRD4 contributes to LPS-induced macrophage senescence and promotes progression of atherosclerosis-associated lipid uptake

作者：Hui Wang, Haiping Fu, Ruigong Zhu, Xuan Wu, Xian Ji, Xuesong Li, Hong Jiang, Zhe Lin, Xin Tang, Shixiu Sun, Jiajing Chen, Xin Wang, Qingguo Li, Yong Ji, Hongshan Chen · 发表于：Aging · 年份：2020 · DOI：10.18632/aging.103200 · 被引用次数：94 · 研究领域：Protein Degradation and Inhibitors、Chromatin Remodeling and Cancer

) mouse peritoneal macrophages, and human peripheral blood mononuclear cells (PBMCs). We found Lipopolysaccharide (LPS) could induce the formation of senescent macrophages, which was typified by the morphological changes, senescence-associated secretory phenotype (SASP) secretory, and persistent DNA damage response. Mechanistically, bromodomain-containing protein 4 (BRD4), a chromosomal binding protein related to gene expression, was found to play a key role in the pathological process, which could offer new therapeutic perspectives. Inhibition of BRD4 by siBRD4 or inhibitors such as JQ-1 or I-BET762 prevented the aging of macrophages and lipid accumulation in the LPS-induced senescent macrophages by decreasing expression of SASP in autocrine and paracrine senescence. These findings have significant implications for the understanding of the pathobiology of age-associated diseases and may guide future studies on targeted clinical drug therapy.