TY - JOUR
T1 - Intestinal adaptation is enhanced by epidermal growth factor independent of increased ileal epidermal growth factor receptor expression
AU - Helmrath, Michael A.
AU - Shin, Cathy E.
AU - Erwin, Christopher R.
AU - Warner, Brad W.
N1 - Funding Information:
From the Division of Pediatric Surgery, Children’s Hospital Medical Center; Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH. Presented at the 1997 Annual Meeting of the Section on Surgery of the American Academy of Pediatrics, New Orleans, Louisiana, October 31.November 2,1997. Supported by a Trustees Grantfrom the Children k Hospital Research Foundation, Children’s Hospital Medical Center; Cincinnati OH (Dr Warner-grant recipient). Address reprint requests to Brad W Warnec MD, Division of Pediatric Surgery, Children’s Hospital Medical Centel; 3333 Burnet Ave, Cincinnati OH 45229.3039. Copyright 0 1998 by WB. Saunders Company 0022.3468/98/3307-0005$03.00/O (2.21 + 0.002 mg/cm Sham v2.97 i 0.25 mg/cm Sham + EGF; P< .05). After SBR, adaptation resulted in increased ileal protein content (4.45 ? 0.27 mg/cm), which was substantially boosted by EGF (5.98 i 0.39 mg/cm; P < .05). No differences were detected in ileal EGF receptor mRNA or protein expression between Sham or SBR groups that did not receive EGF. However, EGF significantly enhanced the expression ileal EGF receptor mRNA to an equal extent after both and SBR (approximately threefold). The magnitude increase in EGF receptor protein (four-to sixfold) in both EGF groups as shown by Western blotting.
PY - 1998/7
Y1 - 1998/7
N2 - Background/Purpose: Intestinal adaptation after massive small bowel resection (SBR) is augmented by epidermal growth factor (EGF) via an unknown mechanism. We recently have observed that EGF increases the expression of EGF receptor mRNA and protein content in the remnant ileum after SBR. The purpose of this study was to determine whether the magnitude of EGF-induced receptor expression correlates with intestinal adaptation. Methods: A 50% proximal SBR or sham operation (bowel transection with reanastomosis) was performed on male ICR mice. Animals from each group were then selected randomly to receive either human recombinant EGF (150 μg/kg/d) or saline by twice daily intraperitoneal injections. The remnant ileum was harvested at 1 week, and parameters of adaptation measured as changes in protein content. Ileal EGF receptor mRNA was quantitated using a ribonuclease protection assay. Changes in the expression ileal EGF receptor protein were determined by Western blot after immunoprecipitation. Comparisons of mean values between groups was performed using analysis of variance (ANOVA) and a P value of less 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), which was substantially boosted by EGF (5.98 ± 0.39 mg/cm; P < .05). No differences were detected in ileal EGF receptor mRNA or protein expression between Sham or SBR groups that did not receive EGF. However, EGF significantly enhanced the expression of ileal EGF receptor mRNA to an equal extent after both sham and SBR (approximately threefold). The magnitude of this increase in EGF receptor protein (four- to sixfold) was similar in both EGF groups as shown by Western blotting. Conclusions: Changes in ileal EGF receptor expression are not mandatory for adaptation 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 beneficial effect of EGF during adaptation is likely caused by other factors in addition to increased receptor expression.
AB - Background/Purpose: Intestinal adaptation after massive small bowel resection (SBR) is augmented by epidermal growth factor (EGF) via an unknown mechanism. We recently have observed that EGF increases the expression of EGF receptor mRNA and protein content in the remnant ileum after SBR. The purpose of this study was to determine whether the magnitude of EGF-induced receptor expression correlates with intestinal adaptation. Methods: A 50% proximal SBR or sham operation (bowel transection with reanastomosis) was performed on male ICR mice. Animals from each group were then selected randomly to receive either human recombinant EGF (150 μg/kg/d) or saline by twice daily intraperitoneal injections. The remnant ileum was harvested at 1 week, and parameters of adaptation measured as changes in protein content. Ileal EGF receptor mRNA was quantitated using a ribonuclease protection assay. Changes in the expression ileal EGF receptor protein were determined by Western blot after immunoprecipitation. Comparisons of mean values between groups was performed using analysis of variance (ANOVA) and a P value of less 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), which was substantially boosted by EGF (5.98 ± 0.39 mg/cm; P < .05). No differences were detected in ileal EGF receptor mRNA or protein expression between Sham or SBR groups that did not receive EGF. However, EGF significantly enhanced the expression of ileal EGF receptor mRNA to an equal extent after both sham and SBR (approximately threefold). The magnitude of this increase in EGF receptor protein (four- to sixfold) was similar in both EGF groups as shown by Western blotting. Conclusions: Changes in ileal EGF receptor expression are not mandatory for adaptation 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 beneficial effect of EGF during adaptation is likely caused by other factors in addition to increased receptor expression.
KW - EGF receptor expression
KW - Enterectomy
KW - Epidermal growth factor
KW - Intestinal adaptation
KW - Intestinal resection
KW - Mice
KW - Receptor
KW - Short bowel syndrome
UR - http://www.scopus.com/inward/record.url?scp=0031820254&partnerID=8YFLogxK
U2 - 10.1016/S0022-3468(98)90518-8
DO - 10.1016/S0022-3468(98)90518-8
M3 - Article
C2 - 9694081
AN - SCOPUS:0031820254
SN - 0022-3468
VL - 33
SP - 980
EP - 985
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
IS - 7
ER -