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Regulation of the Paneth cell niche by exogenous L ‐arginine couples the intestinal stem cell function
Author(s) -
Hou Qihang,
Dong Yuanyang,
Yu Qinghua,
Wang Bo,
Le Shen,
Guo Yuming,
Zhang Bingkun
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902573rr
Subject(s) - paneth cell , stem cell , wnt signaling pathway , microbiology and biotechnology , arginine , biology , wnt3a , niche , chemistry , signal transduction , biochemistry , small intestine , amino acid
Although previous studies show that exogenous nutrients regulate the stem cell function, little is known about the effects of L ‐arginine on intestinal stem cells (ISCs). In this study, we utilize mice, small intestinal (SI) organoids, and ISC‐Paneth cell co‐cultured models to clarify the role of L ‐arginine in ISC function. We find that exogenous L ‐arginine is essential for ISCs proliferation and intestinal epithelial renewal. Our data show that Paneth cells, a critical component of the ISCs niche, augment the ISCs function in response to L ‐arginine. Moreover, enhanced the expression of Wnt3a in Paneth cells, which is a ligand of the Wnt/β‐catenin signaling pathway, mediates the effects of L ‐arginine on ISCs function. Pre‐treatment with L ‐arginine enhances the ISCs pool and protects the gut in response to injury provoked by murine tumor necrosis factor α (TNF‐α) and 5‐Fluorouracil (5‐FU). Our findings establish that the regulation of Wnt3a in the Paneth cell niche by exogenous L ‐arginine couples ISCs function and favours a model in which the ISCs niche couples the nutrient levels to ISCs function.