INTESTINAL ADAPTATION IS ENHANCED BY EPIDERMAL GROWTH-FACTOR INDEPENDENT OF INCREASED ILEAL EPIDERMAL GROWTH-FACTOR RECEPTOR EXPRESSION

Background/Purpose: Intestinal adaptation after massive small bowel re section (SBR) is augmented by epidermal growth factor (EGF) via an unk nown mechanism. We recently have observed that EGF increases the expre ssion of EGF receptor mRNA and protein content in the remnant ileum af ter SBR. The purpose of this study was to determine whether the magnit ude of EGF-induced receptor expression correlates with intestinal adap tation. Methods: A 50% proximal SBR or sham operation (bowel transecti on with reanastomosis) was performed on male ICR mice. Animals from ea ch group were then selected randomly to receive either human recombina nt EGF (150 mu g/kg/d) or saline by twice daily intraperitoneal inject ions. The remnant ileum was harvested at 1 week, and parameters of ada ptation measured as changes in protein content. Ileal EGF receptor mRN A was quantitated using a ribonuclease protection assay. Changes in th e expression ileal EGF receptor protein were determined by Western blo t after immunoprecipitation. Comparisons of mean values between groups was performed using analysis of variance (ANOVA) and a P value of les s than .05 was considered significant. Values are presented as mean +/ - SEM. Results. EGF was mitogenic to the ileum after sham operation as monitored by increases in ileal protein content (2.21 +/- 0.002 mg/cm Sham v2.97 +/- 0.25 mg/cm Sham + EGF; P < .05). After SBR, adaptation resulted in increased ileal protein content (4.45 +/- 0.27 mg/cm), wh ich was substantially boosted by EGF (5.98 +/- 0.39 mg/cm; P < .05). N o differences were detected in ileal EGF receptor mRNA or protein expr ession between Sham or SBR groups that did not receive EGF. However, E GF significantly enhanced the expression of ileal EGF receptor mRNA to an equal extent after both sham and SBR (approximately threefold). Th e magnitude of this increase in EGF receptor protein (four- to sixfold ) was similar in both EGF groups as shown by Western blotting. Conclus ions: Changes in ileal EGF receptor expression are not mandatory for a daptation to occur. EGF upregulates the expression of mRNA and protein for its own intestinal receptor in vivo. Because EGF-induced receptor expression was comparable after both SBR and Sham operation, the bene ficial effect of EGF during adaptation is likely caused by other facto rs in addition to increased receptor expression. J Pediatr Surg 33:980 -985. Copyright (C) 1998 by W.B. Saunders Company.