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.
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.
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.
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.
Key words
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Article info
Publication history
Accepted:
March 8,
2013
Received:
February 14,
2013
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
