巨噬细胞
生物
细胞生物学
炎症性肠病
组蛋白H3
表观遗传学
炎症
免疫系统
组蛋白
癌症研究
免疫学
生物化学
医学
疾病
基因
体外
病理
作者
Shixin Duan,Xinyi Lou,Shiyi Chen,Huimin Jiang,Dongxin Chen,Ranyu Yin,Mengkai Li,Yunjiu Gou,Wenjuan Zhao,Lei Sun,Feng Qian
标识
DOI:10.1016/j.apsb.2023.09.012
摘要
Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.
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