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

World J Gastroenterol. 2012 Apr 14;18(14):1579-89. doi: 10.3748/wjg.v18.i14.1579.


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: Chromogranin A; Enteroendocrine cells; Intestinal epithelial cell specification; Phosphatase and tensin homolog.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Chromogranin A / metabolism*
  • Enteroendocrine Cells / cytology*
  • Gastric Inhibitory Polypeptide / metabolism
  • Gene Expression Profiling*
  • Ghrelin / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / cytology*
  • Mice
  • Mice, Transgenic
  • PTEN Phosphohydrolase / physiology*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • Chromogranin A
  • Ghrelin
  • RNA, Messenger
  • chromogranin A, mouse
  • Gastric Inhibitory Polypeptide
  • PTEN Phosphohydrolase
  • Pten protein, mouse