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Epidermal growth factor upregulates the expression of its own intestinal receptor after small bowel resection
M A Helmrath1, C E Shin, C R Erwin
1Children's Hospital Medical Center, Department of Surgery, University of Cinncinnati College of Medicine, OH 45229-3039, USA.
Background/Purpose:
Epidermal growth factor (EGF) binds to its enterocyte receptor and enhances intestinal adaptation after massive small bowel resection (SBR). To ascertain the mechanism for enhanced adaptation by EGF, we sought to determine the effect of EGF administration on in vivo expression of the intestinal EGF receptor after SBR.
Methods:
Male ICR mice underwent a 50% proximal SBR and then were assigned randomly to EGF (150 microg/kg/d) or saline by twice daily intraperitoneal injection. After 3 days, the ileum was harvested and total protein and DNA content were measured. Northern hybridization and a ribonuclease protection assay were used to detect qualitative and quantitative expression of EGF receptor mRNA. The remaining ileum was pooled for each group and Western blotting used to determine expression of EGF receptor protein.
Results:
EGF augmented adaptation after SBR as monitored by significant 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 microg/cm EGF; P<.001) content. Northern blotting results showed a marked (>fivefold) increase in ileal EGF receptor mRNA, which was confirmed with the ribonuclease protection assay. Administration of EGF after SBR induced a similar expression of EGF receptor protein.
Conclusions:
EGF enhanced intestinal adaptation after SBR. This augmented response is associated with increased ileal expression of EGF receptor mRNA and protein. Increased EGF receptor expression and subsequent enhanced ligand/ receptor activity may be one important mechanism for the beneficial effect of EGF administration during intestinal adaptation.