TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [scRNA-seq]
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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资源简介：
TNF-mediated macrophage polarization is important for inflammatory disease pathogenesis, but mechanisms that regulate polarization are not well understood. Transcriptomic and epigenomic analysis of the TNF response in primary human macrophages revealed late phase activation of SREBP2, the master regulator of cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of SREBP2 occupancy to include binding to and activation of inflammatory and interferon response genes independently of its functions in sterol metabolism. Genetic ablation of SREBP function shifted the balance of macrophage polarization from M1 to an M2-like reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP improved skin wound healing under homeostatic and chronic inflammatory conditions. Our results identify a new function and mechanism of action for SREBP2 in augmenting TNF-induced M1 macrophage polarization and inflammation, and open therapeutic avenues for promoting wound repair.
提供机构：
Ulsan National Institute of Science and Technology
创建时间：
2022-02-20
