Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2017; 23(28): 5127-5145
Published online Jul 28, 2017. doi: 10.3748/wjg.v23.i28.5127
Involvement of CRF2 signaling in enterocyte differentiation
Benjamin Ducarouge, Marjolaine Pelissier-Rota, Rebecca Powell, Alain Buisson, Bruno Bonaz, Muriel Jacquier-Sarlin
Benjamin Ducarouge, Equipe de l’apoptose, du cancer et du développement, Centre Léon Bérard, F-69008 Lyon, France
Marjolaine Pelissier-Rota, Rebecca Powell, Alain Buisson, Bruno Bonaz, Muriel Jacquier-Sarlin, Equipes des “Neuropathologies et Dysfonctions synaptiques” et du “Stress et des interactions neurodigestives”, Université Grenoble Alpes, F-38000 Grenoble, France
Marjolaine Pelissier-Rota, Rebecca Powell, Alain Buisson, Bruno Bonaz, Muriel Jacquier-Sarlin, Equipes des “Neuropathologies et dysfonctions synaptiques” et du “Stress et des interactions neurodigestives”, Université Grenoble Alpes and Grenoble Institut des Neurosciences-Inserm U1216, F-38000 Grenoble, France
Bruno Bonaz, Service d’hépato-gastroentérologie, Centre Hospitalier Universitaire de Grenoble, F-38000 Grenoble, France
Author contributions: Ducarouge B, Pelissier-Rota M, Powell R, Buisson A, Bonaz B and Jacquier-Sarlin M substantially contributed to the conception and design of the study, acquisition, analysis and interpretation of data; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Supported by grants from Association pour la Recherche sur le Cancer, Ligue Nationale contre le Cancer, No. GEFLUC and No. ESPOIR.
Institutional review board statement: The study was reviewed and approved by the “Grenoble Institute of Neurosciences” Institutional Review Board.
Institutional animal care and use committee statement: Animal experimentation was carried out in accordance with the European Community Council directives of November 24, 1986 (86/609/EEC) and with the French guidelines on the use of living animals in scientific investigations with the approval of the “Grenoble Institute of Neurosciences ethical committee”.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exist.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Muriel Jacquier-Sarlin, PhD, Assistant Professor, Equipes des “Neuropathologies et dysfonctions synaptiques” et du “Stress et des interactions neurodigestives”, Université Grenoble Alpes and Grenoble Institut des Neurosciences-Inserm U1216, Site Santé BP 170 La Tronche, F-38000 Grenoble, France. muriel.jacquier-sarlin@univ-grenoble-alpes.fr
Telephone: +33-456-520651 Fax: +33-456-520554
Received: January 30, 2017
Peer-review started: February 8, 2017
First decision: April 5, 2017
Revised: May 6, 2017
Accepted: July 12, 2017
Article in press: July 12, 2017
Published online: July 28, 2017
Core Tip

Core tip: Stress is recognized to participate in the development and/or aggravation of gastrointestinal (GI) disorders mainly by altering intestinal epithelial functions. This occurs partly through the deregulation of neuromediator secretion, but their activity on enterocyte differentiation remains not totally understood. We found that expression of corticotropin releasing factor receptor 2 (CRF2), a stress ligand receptor is inversely correlated to the differentiation status of colon cell lines. We thus investigated the effect of CRF2 signaling on intestinal epithelial differentiation using Ucn3 agonist treatments applied to different cancer cell lines that mimic this process. We identified that CRF2 activation affect both the early steps of differentiation and an established differentiated state, by down-regulating transcription factors such as krüppel-like factor 4. This effect is correlated with alterations of epithelial permeability and cellular adhesion junctions. Our results argue that CFR2-induced alterations of enterocyte differentiation may contribute to stress-mediated barrier dysfunction and the development of GI disorders.