FAM76B regulates PI3K/Akt/NF-κB-mediated M1 macrophage polarization by influencing the stability of PIK3CD mRNA

被引：6

作者：

Wang, Juan ^{[1
,2
]}

Zhao, Xinyue ^{[1
]}

Wang, Qizhi ^{[1
]}

Zheng, Xiaojing ^{[1
]}

Simayi, Dilihumaer ^{[1
]}

Zhao, Junli ^{[1
]}

Yang, Peiyan ^{[1
]}

Mao, Qinwen ^{[3
]}

Xia, Haibin ^{[1
]}

机构：

[1] Shaanxi Normal Univ, Coll Life Sci, Dept Biochem, Lab Gene Therapy, 199 South Changan Rd, Xian 710062, Shaanxi, Peoples R China

[2] Ningxia Med Univ, Sch Basic Med Sci, Dept Pathol, Yinchuan 750004, Peoples R China

[3] Univ Utah, Huntsman Canc Inst, Dept Pathol, 2000 Circle Hope Dr, Salt Lake City, UT 84112 USA

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2024年 / 81卷 / 01期

基金：

中国国家自然科学基金;

关键词：

FAM76B; Macrophage polarization; PI3K; Akt; Inflammatory bowel disease; INFLAMMATORY-BOWEL-DISEASE; TRANSCRIPTIONAL REGULATION; NEGATIVE REGULATION; ACTIVATION; COLITIS; PATHWAY; EXPRESSION; PROTECTS; KINASE; MODEL;

D O I：

10.1007/s00018-024-05133-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Macrophage polarization is closely related to inflammation development, yet how macrophages are polarized remains unclear. In our study, the number of M1 macrophages was markedly increased in Fam76b knockout U937 cells vs. wild-type U937 cells, and FAM76B expression was decreased in M1 macrophages induced from different sources of macrophages. Moreover, Fam76b knockout enhanced the mRNA and protein levels of M1 macrophage-associated marker genes. These results suggest that FAM76B inhibits M1 macrophage polarization. We then further explored the mechanism by which FAM76B regulates macrophage polarization. We found that FAM76B can regulate PI3K/Akt/NF-kappa B pathway-mediated M1 macrophage polarization by stabilizing PIK3CD mRNA. Finally, FAM76B was proven to protect against inflammatory bowel disease (IBD) by inhibiting M1 macrophage polarization through the PI3K/Akt/NF-kappa B pathway in vivo. In summary, FAM76B regulates M1 macrophage polarization through the PI3K/Akt/NF-kappa B pathway in vitro and in vivo, which may inform the development of future therapeutic strategies for IBD and other inflammatory diseases.

引用

页数：19