Epithelial IGF1R is dispensable for IGF2 mediated enhanced intestinal adaptation in retinoblastoma-deficient mice.

Autor: Sun RC; Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Choi PM; Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Diaz-Miron JL; Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Sommovilla J; Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Guo J; Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Erwin CR; Division of Pediatric Surgery, St Louis Children's Hospital, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA., Warner BW; 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.
Jazyk: angličtina
Zdroj: Journal of pediatric surgery [J Pediatr Surg] 2017 Jun; Vol. 52 (6), pp. 1026-1030. Date of Electronic Publication: 2017 Mar 18.
DOI: 10.1016/j.jpedsurg.2017.03.030
Abstrakt: Purpose: 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.
Conclusion: 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.
Level of Evidence: Animal study - not clinical.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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