title: Both epidermal growth factor and insulin-like growth factor receptors are dispensable for structural intestinal adaptation.
abstract: OBJECTIVE
  Intestinal adaptation structurally represents increases in crypt depth and villus height in response to small bowel resection (SBR). Previously, we found that neither epidermal growth factor receptor (EGFR) nor insulin-like growth factor 1 receptor (IGF1R) function was individually required for normal adaptation. In this study, we sought to determine the effect of disrupting both EGFR and IGF1R expression on resection-induced adaptation.
  
  
  METHODS
  Intestinal-specific EGFR and IGF1R double knockout mice (EGFR/IGF1R-IKO) (n=6) and wild-type (WT) control mice (n=7) underwent 50% proximal SBR. On postoperative day (POD) 7, structural adaptation was scored by measuring crypt depth and villus height. Rates of crypt cell proliferation, apoptosis, and submucosal capillary density were also compared.
  
  
  RESULTS
  After 50% SBR, normal adaptation occurred in both WT and EGFR/IGF1R-IKO. Rates of proliferation and apoptosis were no different between the two groups. The angiogenic response was less in the EGFR/IGF1R-IKO compared to WT mice.
  
  
  CONCLUSIONS
  Disrupted expression of EGFR and IGF1R in the intestinal epithelial cells does not affect resection-induced structural adaptation but attenuates angiogenesis after SBR. These findings suggest that villus growth is driven by receptors and pathways that occur outside the epithelial cell component, while angiogenic responses may be influenced by epithelial-endothelial crosstalk.
authors.affiliation: Division of Pediatric Surgery; St Louis Children's Hospital, Department of Surgery; Washington University School of Medicine, St. Louis, MO.
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.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Diaz-Miron
authors.affiliation: Division of Pediatric Surgery; St Louis Children's Hospital, Department of Surgery; Washington University School of Medicine, St. Louis, MO.
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.
authors.forename: Joshua
authors.initials: J
authors.lastname: Sommovilla
authors.affiliation: Division of Pediatric Surgery; St Louis Children's Hospital, Department of Surgery; Washington University School of Medicine, St. Louis, MO.
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.
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. 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; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply / Q000502:physiology* / Q000601:surgery*; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: D066246:ErbB Receptors; D017526:Receptor, IGF Type 1
keywords: Epidermal growth factor receptor; Insulin-like growth factor 1 receptor; Intestinal adaptation; Short gut syndrome
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