Epithelial IGF1R is dispensable for IGF2 mediated enhanced intestinal adaptation in retinoblastoma-deficient mice.
OBJECTIVE
Previously, we demonstrated enhanced adaptation after small bowel resection (SBR) in intestinal-specific retinoblastoma (Rb)-deficient mice along with elevated levels of insulin-like growth factor 2 (IGF2) expression within the villi. The purpose of this study was to verify that the insulin-like growth factor 1 receptor (IGF1R) plays a role in this phenomenon.


METHODS
Inducible and intestinal specific Rb and IGF1R double knockout mice (iRb/IGF1R-IKO) (n=4) and Rb single knockout mice (iRb-IKO) (n=5) underwent 50% mid SBR. On post-operative day 28, mice were harvested, and structural adaptation was measured as changes in crypt depth and villus height. Rates of enterocyte proliferation were recorded. IGF2 expression within the remnant villi was measured via RT-PCR.


RESULTS
Both iRb-IKO and iRb/IGF1R-IKO mice demonstrated enhanced adaptation with at least a 45% increase in both crypt depth and villus height in the proximal and distal remnant bowel. Both groups showed elevation of IGF2 expression in the remnant villi, but there were no differences between the two groups.


CONCLUSIONS
Epithelial IGF1R is dispensable for IGF2-mediated enhanced intestinal adaptation in retinoblastoma-deficient mice. Our findings suggest that IGF2 signals for enhanced adaptation in cells outside of the epithelium. Further investigation is needed to study the IGF2/IGF1R signaling interaction within the mesenchyme.


METHODS
Animal study - not clinical.
Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Raphael C
RC
Sun
Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Pamela M
PM
Choi
Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jose L
JL
Diaz-Miron
Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Joshua
J
Sommovilla
Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jun
J
Guo
Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Christopher R
CR
Erwin
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.
Brad W
BW
Warner
D000222:Adaptation, Physiological; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D007421:Intestine, Small / Q000378:metabolism / Q000502:physiology / Q000601:surgery*; D051379:Mice; D018345:Mice, Knockout; D011184:Postoperative Period; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000172:deficiency*; D012778:Short Bowel Syndrome / Q000378:metabolism* / Q000503:physiopathology
D015415:Biomarkers; C513121:IGF2 protein, mouse; D016160:Retinoblastoma Protein; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1
Insulin-like growth factor 1 receptor; Insulin-like growth factor-2; Intestinal adaptation; Retinoblastoma deletion; Short gut syndrome