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IGF-2 mediates intestinal mucosal hyperplasia in retinoblastoma protein (Rb)-deficient mice.
- Source :
-
Journal of pediatric surgery [J Pediatr Surg] 2013 Jun; Vol. 48 (6), pp. 1340-7. - Publication Year :
- 2013
-
Abstract
- Purpose: We have previously demonstrated a hyperplastic phenotype when Rb expression was disrupted within the intestinal epithelium. These findings mimic resection-induced adaptation suggesting a possible mechanistic role for Rb during adaptation. The purpose of the present study was to elucidate a mechanism for how Rb deficiency induces intestinal hyperplasia.<br />Methods: Enterocytes isolated from intestine-specific Rb knockout mice (Rb-IKO) underwent a microarray to elucidate their gene expression profile. IGF2 expression was significantly elevated, which was subsequently confirmed by RT-PCR and in situ mRNA hybridization. Mice with deficient expression of IGF2 or its receptor IGF1R were therefore crossed with Rb-IKO mice to determine the significance of IGF2 in mediating the Rb-IKO intestinal phenotype.<br />Results: Expression of IGF2 was significantly elevated in villus enterocytes of Rb-IKO mice. The mucosal hyperplasia in Rb-IKO mice was reversed when either IGF2 or IGF1R expression was genetically disrupted in Rb-IKO mice.<br />Conclusion: IGF-2 expression is significantly elevated in villus enterocytes and is required for the hyperplastic intestinal mucosal phenotype of Rb-IKO mice. The trophic effects of IGF2 require intact IGF1R signaling within the intestinal epithelium. These findings reveal novel regulatory roles for Rb in expanding intestinal mucosal surface area.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biomarkers metabolism
Blotting, Western
Cell Proliferation
Enterocytes metabolism
Enterocytes pathology
Gene Expression Profiling
Hyperplasia
In Situ Hybridization
Intestinal Mucosa metabolism
Mice
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
Receptor, IGF Type 1 metabolism
Reverse Transcriptase Polymerase Chain Reaction
Insulin-Like Growth Factor II metabolism
Intestinal Mucosa pathology
Retinoblastoma Protein deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1531-5037
- Volume :
- 48
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of pediatric surgery
- Publication Type :
- Academic Journal
- Accession number :
- 23845628
- Full Text :
- https://doi.org/10.1016/j.jpedsurg.2013.03.042