IGF-2 mediates intestinal mucosal hyperplasia in retinoblastoma protein (Rb)-deficient mice

Pamela Choi, Jun Guo, Christopher R. Erwin, Brad W. Warner

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Purpose We have previously demonstrated a hyperplastic phenotype when Rb expression was disrupted within the intestinal epithelium. These findings mimic resection-induced adaptation suggesting a possible mechanistic role for Rb during adaptation. The purpose of the present study was to elucidate a mechanism for how Rb deficiency induces intestinal hyperplasia. Methods Enterocytes isolated from intestine-specific Rb knockout mice (Rb-IKO) underwent a microarray to elucidate their gene expression profile. IGF2 expression was significantly elevated, which was subsequently confirmed by RT-PCR and in situ mRNA hybridization. Mice with deficient expression of IGF2 or its receptor IGF1R were therefore crossed with Rb-IKO mice to determine the significance of IGF2 in mediating the Rb-IKO intestinal phenotype. Results Expression of IGF2 was significantly elevated in villus enterocytes of Rb-IKO mice. The mucosal hyperplasia in Rb-IKO mice was reversed when either IGF2 or IGF1R expression was genetically disrupted in Rb-IKO mice. Conclusion IGF-2 expression is significantly elevated in villus enterocytes and is required for the hyperplastic intestinal mucosal phenotype of Rb-IKO mice. The trophic effects of IGF2 require intact IGF1R signaling within the intestinal epithelium. These findings reveal novel regulatory roles for Rb in expanding intestinal mucosal surface area.

Original languageEnglish
Pages (from-to)1340-1347
Number of pages8
JournalJournal of Pediatric Surgery
Volume48
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Insulin-like growth factor 1 receptor
  • Insulin-like growth factor-2
  • Retinoblastoma protein
  • Small bowel adaptation

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