Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis

Keqiang Chen, Mingyong Liu, Ying Liu, Teizo Yoshimura, Wei Shen, Yingying Le, Scott Durum, Wanghua Gong, Chunyan Wang, Ji Liang Gao, Philip M. Murphy, Ji Ming Wang

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Commensal bacteria and their products provide beneficial effects to the mammalian gut by stimulating epithelial cell turnover and enhancing wound healing, without activating overt inflammation. We hypothesized that N-formylpeptide receptors, which bind bacterial N-formylpeptides and are expressed by intestinal epithelial cells, may contribute to these processes. Here we report that formylpeptide receptor-2 (FPR2), which we show is expressed on the apical and lateral membranes of colonic crypt epithelial cells, mediates N-formylpeptide- dependent epithelial cell proliferation and renewal. Colonic epithelial cells in FPR2-deficient mice displayed defects in commensal bacterium-dependent homeostasis as shown by the absence of responses to N-formylpeptide stimulation, shortened colonic crypts, reduced acute inflammatory responses to dextran sulfate sodium (DSS) challenge, delayed mucosal restoration after injury, and increased azoxymethane-induced tumorigenesis. These results indicate that FPR2 is critical in mediating homeostasis, inflammation, and epithelial repair processes in the colon.

Original languageEnglish
Pages (from-to)1694-1704
Number of pages11
JournalJournal of Clinical Investigation
Volume123
Issue number4
DOIs
Publication statusPublished - Apr 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Chen, K., Liu, M., Liu, Y., Yoshimura, T., Shen, W., Le, Y., Durum, S., Gong, W., Wang, C., Gao, J. L., Murphy, P. M., & Wang, J. M. (2013). Formylpeptide receptor-2 contributes to colonic epithelial homeostasis, inflammation, and tumorigenesis. Journal of Clinical Investigation, 123(4), 1694-1704. https://doi.org/10.1172/JCI65569