title: Insulin-like growth factor 2 and its enterocyte receptor are not required for adaptation in response to massive small bowel resection.
abstract: OBJECTIVE
  Enhanced structural features of resection-induced intestinal adaptation have been demonstrated following the administration of multiple different growth factors and peptides. Among these, the insulin-like growth factor (IGF) system has been considered to be significant. In this study, we employ mutant mouse strains to directly test the contribution of IGF2 and its enterocyte receptor (IGF1R) toward the adaptation response to massive small bowel resection (SBR).
  
  
  METHODS
  IGF2-knockout (IGF2-KO) (n=8) and intestine specific IGF1R-knockout mice (IGF1R-IKO) (n=9) and their wild type (WT) littermates (n=5, n=7, respectively) underwent 50% proximal SBR. At post-operative day 7, structural adaptation was measured as crypt depth and villus height. Rates of enterocyte proliferation and apoptosis were also recorded.
  
  
  RESULTS
  The successful deletion of IGF2 and IGF1R expression in the enterocytes was confirmed by RT-PCR and Western blot, respectively. Normal adaptation occurred in both IGF2-KO and IGF1R-IKO mice after 50% SBR. Post-operative rates of proliferation and apoptosis in both IGF2-KO and IGF1R-IKO mice were no different than their respective controls.
  
  
  CONCLUSIONS
  IGF2 and functional IGF1R signaling in enterocytes are both dispensable for resection-induced adaptation responses. The mechanism for IGF-stimulation of intestinal adaptation may involve other ligands or cellular compartments within the intestine.
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Raphael C
authors.initials: RC
authors.lastname: Sun
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Choi
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Erwin
authors.affiliation: Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: brad.warner@wustl.edu.
authors.forename: Brad W
authors.initials: BW
authors.lastname: Warner
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D004195:Disease Models, Animal; D020895:Enterocytes / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics*; D007413:Intestinal Mucosa; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012778:Short Bowel Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D012313:RNA; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1
keywords: Insulin-like growth factor 1 receptor; Insulin-like growth factor-2; Intestinal adaptation; Short gut syndrome