Dual regulatory role for phosphatase and tensin homolog in specification of intestinal endocrine cell subtypes

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. (C) 2012 Baishideng. All rights reserved.