title: IGF-2 is necessary for retinoblastoma-mediated enhanced adaptation after small-bowel resection.
abstract: Previously, we have demonstrated that genetically disrupting retinoblastoma protein (Rb) expression in enterocytes results in taller villi, mimicking resection-induced adaption responses. Rb deficiency also results in elevated insulin-like growth factor-2 (IGF-2) expression in villus enterocytes. We propose that postoperative disruption of Rb results in enhanced adaptation which is driven by IGF-2. Inducible, intestine-specific Rb-null mice (iRbIKO) and wild-type (WT) littermates underwent a 50% proximal small-bowel resection (SBR) at 7-9 weeks of age. They were then given tamoxifen on postoperative days (PODs) 4-6 and harvested on POD 28. The experiment was then repeated on double knockouts of both IGF-2 and Rb (IGF-2 null/iRbIKO). iRbIKO mice demonstrated enhanced resection-induced adaptive villus growth after SBR and increased IGF-2 messenger RNA (mRNA) in ileal villus enterocytes compared to their WT littermates. In the IGF-2 null/iRbIKO double-knockout mice, there was no additional villus growth beyond what was expected of normal resection-induced adaptation. Adult mice in which Rb is inducibly deleted from the intestinal epithelium following SBR have augmented adaptive growth. IGF-2 expression is necessary for enhanced adaptation associated with acute intestinal Rb deficiency.
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, St Louis Children's Hospital, Washington University School of Medicine, One Children's Place, Suite 5S40, St Louis, MO, 63110, USA.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Choi
authors.forename: Raphael C
authors.initials: RC
authors.lastname: Sun
authors.forename: Josh
authors.initials: J
authors.lastname: Sommovilla
authors.forename: Jose
authors.initials: J
authors.lastname: Diaz-Miron
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: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D004195:Disease Models, Animal; D020895:Enterocytes / Q000378:metabolism*; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000473:pathology / Q000601:surgery*; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D020858:Tissue and Organ Harvesting
chemical_list: D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D013629:Tamoxifen; D007335:Insulin-Like Growth Factor II