期刊
CELL REPORTS
卷 27, 期 4, 页码 1176-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.03.028
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资金
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB19000000]
- Ministry of Science and Technology of China [2016YFD0500207, 2016YFC0905902, 2016YFD0500407]
- National Natural Science Foundation of China [81825011, 81630043, 81571617, 81671572, 81571552, 81701569, 31700781, 81801575]
- State Key Laboratory of Cell Biology, SIBCB, CAS [SKL CBKF2013003]
Inflammation, epithelial cell regeneration, macrophage polarization, and gut microbial homeostasis are critical for the pathological processes associated with inflammatory bowel disease (IBD). YAP (Yes-associated protein) is a key component of the Hippo pathway and was recently suggested to promote epithelial cell regeneration for IBD recovery. However, it is unclear how YAP regulates macrophage polarization, inflammation, and gut microbial homeostasis. Although YAP has been shown to promote epithelial regeneration and alleviate IBD, here we show that YAP in macrophages aggravates IBD, accompanied by the production of antimicrobial peptides and changes in gut microbiota. YAP impairs interleukin-4 (IL-4)/IL-13-induced M2 macrophage polarization while promoting lipopolysaccharide (LPS)/interferon gamma (IFN-gamma)-triggered M1 macrophage activation for IL-6 production. In addition, YAP expression is differently regulated during the induction of M2 versus M1 macrophages. This study suggests that fully understanding the multiple functions of YAP in different cell types is crucial for IBD therapy.
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