lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

L-Arginine Enhances Intestinal Stem Cell Function

48 Pages Posted: 8 Mar 2019

See all articles by Qihang Hou

Qihang Hou

China Agricultural University - State Key Laboratory of Animal Nutrition

Qinghua Yu

Nanjing Agricultural University (NAU) - MOE Joint International Research Laboratory of Animal Health and Food Safety

Yuanyang Dong

China Agricultural University - State Key Laboratory of Animal Nutrition

Xiaoxi Lu

Nanjing Agricultural University (NAU) - MOE Joint International Research Laboratory of Animal Health and Food Safety

Lulu Ye

Nanjing Agricultural University (NAU) - MOE Joint International Research Laboratory of Animal Health and Food Safety

Bo Wang

China Agricultural University - State Key Laboratory of Animal Nutrition

Yuming Guo

China Agricultural University - State Key Laboratory of Animal Nutrition

Le Shen

University of Chicago

Bingkun Zhang

China Agricultural University - State Key Laboratory of Animal Nutrition

More...

Abstract

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

Suggested Citation

Hou, Qihang and Yu, Qinghua and Dong, Yuanyang and Lu, Xiaoxi and Ye, Lulu and Wang, Bo and Guo, Yuming and Shen, Le and Zhang, Bingkun, L-Arginine Enhances Intestinal Stem Cell Function (March 6, 2019). Available at SSRN: https://ssrn.com/abstract=3347896

Qihang Hou (Contact Author)

China Agricultural University - State Key Laboratory of Animal Nutrition ( email )

Beijing
China

Qinghua Yu

Nanjing Agricultural University (NAU) - MOE Joint International Research Laboratory of Animal Health and Food Safety ( email )

Nanjing
210095
China

Yuanyang Dong

China Agricultural University - State Key Laboratory of Animal Nutrition

Beijing
China

Xiaoxi Lu

Nanjing Agricultural University (NAU) - MOE Joint International Research Laboratory of Animal Health and Food Safety

Nanjing
210095
China

Lulu Ye

Nanjing Agricultural University (NAU) - MOE Joint International Research Laboratory of Animal Health and Food Safety

Nanjing
210095
China

Bo Wang

China Agricultural University - State Key Laboratory of Animal Nutrition

Beijing
China

Yuming Guo

China Agricultural University - State Key Laboratory of Animal Nutrition

Beijing
China

Le Shen

University of Chicago

1101 East 58th Street
Chicago, IL 60637
United States

Bingkun Zhang

China Agricultural University - State Key Laboratory of Animal Nutrition ( email )

Beijing
China

Click here to go to TheLancet.com

Go to TheLancet.com

Paper statistics

Abstract Views
74
Downloads
18