Regulation of the Paneth cell niche by exogenous <scp>L</scp> ‐arginine couples the intestinal stem cell function
Qihang Hou, Yuanyang Dong, Qinghua Yu, Bo Wang, Le Shen, Yuming Guo, Bingkun Zhang
Abstract
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.