TY - JOUR
T1 - IGF-2 Is Necessary for Retinoblastoma-Mediated Enhanced Adaptation after Small-Bowel Resection
AU - Choi, Pamela M.
AU - Sun, Raphael C.
AU - Sommovilla, Josh
AU - Diaz-Miron, Jose
AU - Guo, Jun
AU - Erwin, Christopher R.
AU - Warner, Brad W.
N1 - Funding Information:
Acknowledgments This work was supported by National Institutes of Health Grants T32 GM008795 (Choi), P30DK52574 Morphology and Murine Models Cores of the Digestive Diseases Research Core Center of the Washington University School of Medicine, and the Children’s Surgical Sciences Institute of the St. Louis Children’s Hospital Foundation. Dr. Choi is also supported by The Marion and Van Black Endowed Pediatric Surgical Research Fellowship.
Publisher Copyright:
© 2014, The Society for Surgery of the Alimentary Tract.
PY - 2014/11
Y1 - 2014/11
N2 - 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.
AB - 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.
KW - Insulin-like growth factor-2
KW - Retinoblastoma protein
KW - Small-bowel adaptation
UR - http://www.scopus.com/inward/record.url?scp=84933501362&partnerID=8YFLogxK
U2 - 10.1007/s11605-014-2586-1
DO - 10.1007/s11605-014-2586-1
M3 - Article
C2 - 25002022
AN - SCOPUS:84933501362
SN - 1091-255X
VL - 18
SP - 1887
EP - 1893
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
IS - 11
ER -