Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 14, 2012; 18(14): 1579-1589
Published online Apr 14, 2012. doi: 10.3748/wjg.v18.i14.1579
Dual regulatory role for phosphatase and tensin homolog in specification of intestinal endocrine cell subtypes
Sébastien AB Roy, Marie-Josée Langlois, Julie C Carrier, François Boudreau, Nathalie Rivard, Nathalie Perreault
Sébastien AB Roy, Marie-Josée Langlois, François Boudreau, Nathalie Rivard, Nathalie Perreault, Canadian Institutes of Health Research Team on Digestive Epithelium, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke J1H 5N4, QC, Canada
Julie C Carrier, Canadian Institutes of Health Research Team on Digestive Epithelium, Service of Gastroenterology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke J1H 5N4, QC, Canada
Author contributions: Carrier JC, Boudreau F, Rivard N and Perreault N designed the research; Roy SAB and Langlois MJ performed the research; all authors analyzed the data; Langlois MJ drafted the paper; Perreault N wrote the paper.
Supported by The Canadian Institutes of Health Research team grant, CTP-82942 to Carrier JC, Boudreau F, Rivard N, Perreault N; Carrier JC, Boudreau F and Perreault N are scholars from the Fonds de la Recherche en Santé du Québec; Rivard N is a recipient of a Canadian Research Chair in Signaling and Digestive Physiopathology; Rivard N, Perreault N, Carrier JC and Boudreau F are members of the FRSQ-funded “Centre de Recherche Clinique Étienne Lebel”
Correspondence to: Nathalie Perreault, PhD, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke J1H 5N4, QC, Canada. nathalie.perreault@usherbrooke.ca
Telephone: +1-819-8206875 Fax: +1-819-5645320
Received: November 24, 2011
Revised: February 6, 2012
Accepted: February 26, 2012
Published online: April 14, 2012
Abstract

AIM: To investigate the impact of phosphatase and tensin homolog (Pten) in the specification of intestinal enteroendocrine subpopulations.

METHODS: Using the Cre/loxP system, a mouse with conditional intestinal epithelial Pten deficiency was generated. Pten mutant mice and controls were sacrificed and small intestines collected for immunofluorescence and quantitative real-time polymerase chain reaction. Blood was collected on 16 h fasted mice by cardiac puncture. Enzyme-linked immunosorbent assay was used to measure blood circulating ghrelin, somatostatin (SST) and glucose-dependent insulinotropic peptide (GIP) levels.

RESULTS: Results show an unexpected dual regulatory role for epithelial Pten signalling in the specification/differentiation of enteroendocrine cell subpopulations in the small intestine. Our data indicate that Pten positively regulates chromogranin A (CgA) expressing subpopulations, including cells expressing secretin, ghrelin, gastrin and cholecystokinin (CCK). In contrast, Pten negatively regulates the enteroendocrine subtype specification of non-expressing CgA cells such as GIP and SST expressing cells.

CONCLUSION: The present results demonstrate that Pten signalling favours the enteroendocrine progenitor to specify into cells expressing CgA including those producing CCK, gastrin and ghrelin.

Keywords: Phosphatase and tensin homolog, Enteroendocrine cells, Intestinal epithelial cell specification, Chromogranin A