2. Academic Validation
  3. YAP Aggravates Inflammatory Bowel Disease by Regulating M1/M2 Macrophage Polarization and Gut Microbial Homeostasis

YAP Aggravates Inflammatory Bowel Disease by Regulating M1/M2 Macrophage Polarization and Gut Microbial Homeostasis

  • Cell Rep. 2019 Apr 23;27(4):1176-1189.e5. doi: 10.1016/j.celrep.2019.03.028.
Xin Zhou 1,  Weiyun Li 1,  Shuang Wang 1,  Panli Zhang 2,  Qiong Wang 3,  Jun Xiao 1,  Chi Zhang 1,  Xin Zheng 1,  Xiaoyan Xu 4,  Shengjie Xue 1,  Lijian Hui 1,  Hongbin Ji 1,  Bin Wei 5,  Hongyan Wang 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Innovation Center for Cell Signaling Network, Shanghai 200031, China.
  • 2 College of Life Sciences, Shanghai University, Shanghai 200444, China.
  • 3 State Key Laboratory of Cell Biology, Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Innovation Center for Cell Signaling Network, Shanghai 200031, China; Institute of Spine Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 4 State Key Laboratory of Cell Biology, Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Innovation Center for Cell Signaling Network, Shanghai 200031, China; Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
  • 5 College of Life Sciences, Shanghai University, Shanghai 200444, China; Cancer Center, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China. Electronic address: weibinwhy@shu.edu.cn.
  • 6 State Key Laboratory of Cell Biology, Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Innovation Center for Cell Signaling Network, Shanghai 200031, China. Electronic address: hongyanwang@sibcb.ac.cn.
PMID: 31018132 DOI: 10.1016/j.celrep.2019.03.028
Abstract

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 γ (IFN-γ)-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.

Keywords

Hippo pathway; IBD; IL-6; YAP; inflammation; inflammatory bowel disease; interleukin-6; macrophage polarization; microbiota.

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