L-Arginine Enhances Intestinal Stem Cell Function
48 Pages Posted: 8 Mar 2019More...
Background: L-arginine preserves intestinal barrier integrity from injury, but underlying mechanisms remain unknown.
Methods: In this study we utilized mice and small intestinal (SI) organoid models to clarify the role of L-arginine on epithelial differentiation of intestinal stem cells (ISCs).
Findings: Here we show that L-arginine significantly increased expansion of ISCs, and Paneth cells in vivo and in vitro. Importantly, L-arginine stimulated ISC proliferation through Wnt/β-catenin signals of Paneth cells. Pre-treatment with L-arginine protected SI organoids in response to damage provoked by murine TNF-α and mice in response to gut injury provoked by a chemotherapy drug (5-FU).
Interpretation: Our results demonstrate that L-arginine stimulated ISCs proliferation through Wnt/β-Catenin pathway activated by Wnt3a secreted by Paneth cells to protect the intestinal epithelial barrier.
Funding Statement: This work was supported by National Key R&D Program of China (2018YFD0500600), the State Key Laboratory of Animal Nutrition (2004DA125184), National Natural Science Foundation of China (31502024), National Basic Research Program of China (973 program 2013CB127302), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Declaration of Interests: There are no conflicts of interest (financial, professional or personal) related to this manuscript.
Ethics Approval Statement: All procedures were performed in accordance with institutional and national guidelines and regulations and were approved by the China Agricultural University Animal Care and Use Committee.
Keywords: L-arginine, intestinal stem cell, Paneth cell, Wnt3a, 5-FU
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