The expression and activation of EGF and c-NEU receptors are increased in enterocytes during intestinal adaptation

Background/Purpose: After massive small bowel resection (SBR), epidermal growth factor (EGF) and its intestinal receptor (EGF-R) play major roles during adaptation. The expression of a homologous enterocyte receptor termed c-neu (c-neu-R) is capable of forming heterodimers with EGF-R to facilitate cellular signaling. The purpose of this study was to determine the expression and activation of EGF-R and c-neu-R during the adaptive intestinal response to SBR. Methods: Male ICR mice underwent either SBR or sham surgery. After 1,3, and 7 days, enterocytes were isolated and protein immunoprecipitated with antibody to either EGF-R or c-neu-R. Receptor protein expression and activation status were determined. Results: When compared with sham operation, the expression and act vat on status of both EGF-R (six- and twofold, respectively) and c-neu-R (nine- and twofold, respectively) were increased substantially in enterocytes from the adapting ileum after SBR by postoperative day 3. Minimal changes were appreciated for either EGF-R or c- neu-R expression or activation in the remnant bowel after enterocyte removal, liver, or kidney. Conclusions: Both the expression and activation status of EGF-R and c-neu-R are increased substantially in enterocytes from the adapting ileum by postoperative day 3 after massive SBR. These changes provide a unique mechanism for the enterocyte to enhance cellular signaling in response to EGF during intestinal adaptation.