title: IGF-2 mediates intestinal mucosal hyperplasia in retinoblastoma protein (Rb)-deficient mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Division of Pediatric Surgery, St Louis Children's Hospital, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Choi
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Erwin
authors.forename: Brad W
authors.initials: BW
authors.lastname: Warner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D020895:Enterocytes / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006965:Hyperplasia; D017403:In Situ Hybridization; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000172:deficiency*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D016160:Retinoblastoma Protein; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1
keywords: Insulin-like growth factor 1 receptor; Insulin-like growth factor-2; Retinoblastoma protein; Small bowel adaptation