EPIDERMAL GROWTH-FACTOR UP-REGULATES THE EXPRESSION OF ITS OWN INTESTINAL RECEPTOR AFTER SMALL-BOWEL RESECTION

Background/Purpose: Epidermal growth factor (EGF) binds to its enteroc yte receptor and enhances intestinal adaptation after massive small bo wel resection (SBR). To ascertain the mechanism for enhanced adaptatio n by EGF, we sought to determine the effect of EGF administration on i n vivo expression of the intestinal EGF receptor after SBR. Methods: M ale ICR mice underwent a 50% proximal SBR and then were assigned rando mly to EGF (150 mu g/kg/d) or saline by twice daily intraperitoneal in jection. After 3 days, the ileum was harvested and total protein and D NA content were measured. Northern hybridization and a ribonuclease pr otection assay were used to detect qualitative and quantitative expres sion of EGF receptor mRNA. The remaining ileum was pooled for each gro up and Western blotting used to determine expression of EGF receptor p rotein. Results: EGF augmented adaptation after SBR as monitored by si gnificant increases in ileal protein (2.7 +/- 0.08 saline versus 3.9 /- 0.17 mg/cm EGF; P < .001) and DNA (55.8 +/- 1.6 saline versus 104 /- 8.4 mu gm/cm EGF; P < .001) content. Northern blotting results show ed a marked (>fivefold) increase in ileal EGF receptor mRNA, which was confirmed with the ribonuclease protection assay. Administration of E GF after SBR induced a similar expression of EGF receptor protein. Con clusions: EGF enhanced intestinal adaptation after SBR. This augmented response is associated with increased ileal expression of EGF recepto r mRNA and protein. Increased EGF receptor expression and subsequent e nhanced ligand/receptor activity may be one important mechanism for th e beneficial effect of EGF administration during intestinal adaptation . Copyright (C) 1998 by W.B. Saunders Company.