Critical roles for EGF receptor signaling during resection-induced intestinal adaptation.
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.
Warner
Brad W
BW
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Department of Surgery, University of Cincinnati College of Medicine, OH 45229-3039, USA. brad.warner@cchmc.org
Erwin
Christopher R
CR
D000222:Adaptation, Physiological; D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery*; D015398:Signal Transduction
D066246:ErbB Receptors