Critical roles for EGF receptor signaling during resection-induced intestinal adaptation

Brad W. Warner, Christopher R. Erwin

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The adaptation response of the remnant gut to massive intestinal resection represents a mitogenic signal involving all bowel wall layers. In the mucosa, this response results in taller villi, deeper crypts, and enhanced enterocyte turnover as gauged by greater rates of both proliferation and apoptosis. Although the exact mechanisms and mediators of this important compensatory response remain incompletely understood, work from this laboratory over the past decade has illuminated a crucial role for intact receptor signaling for a robust response. Using a murine model for intestinal resection, transgenic, null and mutant mouse strains have provided unique experimental paradigms to dissect molecular mechanisms for epidermal growth factor (EGF) receptor-directed influence on adaptation. Stimulation of this receptor is linked with a magnified adaptation response, whereas attenuation of the activity of this receptor is associated with impaired adaptation. EGF receptor activation and expression are both elevated in enterocytes after resection, and salivary levels of EGF-the major ligand for the EGF receptor-are increased. In addition to stimulation of enterocyte proliferation, EGF receptor signaling prevents the typical increase in rates of enterocyte apoptosis, probably by affecting the ratio of expression of both pro- and anti-apoptotic Bcl-2 family members. The key to optimizing care for patients with short gut syndrome will necessarily follow a thorough understanding of intestinal adaptation responses.

Original languageEnglish
Pages (from-to)S68-S73
JournalJournal of pediatric gastroenterology and nutrition
Volume43
Issue number1 SUPPL. 1
DOIs
StatePublished - Jul 2006

Keywords

  • Epidermal growth factor receptor
  • Intestinal adaptation
  • Intestinal failure

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