Intestinal phenotype in mice overexpressing a heparin-binding EGF-like growth factor transgene in enterocytes

Chun Liang Chen, Veela B. Mehta, Hong Yi Zhang, Dana Wu, Iyore Otabor, Andrei Radulescu, Osama N. El-Assal, Jiexiong Feng, Yan Chen, Gail E. Besner

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Primary objective. Heparin-binding EGF-like growth factor (HB-EGF) protects the intestine from damage in animals. Future clinical trials of HB-EGF may involve administration of repeated doses of HB-EGF. Since HB-EGF activates EGF receptors which have been implicated in tumor development, we examined the effects of HB-EGF overexpression in the intestine.Research design. We generated transgenic (TG) mice in which the human HB-EGF gene is driven by the villin promoter to overexpress HB-EGF along the crypt-villous axis from the duodenum to the colon.Results. HB-EGF TG mice have increased enterocyte proliferation balanced by increased enterocyte apoptosis. Despite prolonged overexpression of HB-EGF, no evidence of intestinal hyperplasia or tumor formation occurs. Although HB-EGF TG mice have no significant phenotypic alterations under basal conditions, they have increased resistance to intestinal injury.Conclusions. Prolonged intestinal HB-EGF overexpression results in no significant phenotypic alterations under basal conditions, but confers protection against intestinal injury.

Original languageEnglish (US)
Pages (from-to)82-97
Number of pages16
JournalGrowth Factors
Volume28
Issue number2
DOIs
StatePublished - Apr 2010
Externally publishedYes

Keywords

  • HB-EGF
  • Injury
  • Intestine
  • Transgenic
  • Villin promoter
  • Villous

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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