A serum factor after intestinal resection stimulates epidermal growth factor receptor signaling and proliferation in intestinal epithelial cells.
BACKGROUND
In vivo, intestinal adaptation after massive small bowel resection (SBR) requires a functional epidermal growth factor (EGF) receptor (EGFR). In vitro studies have shown that serum from mice after SBR induces rat intestinal epithelial cells to proliferate. This study tested the hypothesis that the proliferative response to SBR serum is mediated by EGFR signaling.


METHODS
Serum was collected from male Sprague-Dawley rats 7 days after 75% SBR or sham operation. Rat intestinal epithelial cells were incubated in the presence of sham or SBR serum. Total EGFR expression and phosphorylation of several EGFR downstream pathways were determined by Western blotting. In other experiments, a specific EGFR inhibitor (ZD1839) was added and cell growth determined over 5 days.


RESULTS
SBR serum significantly increased total EGFR expression (3-fold) over sham operation and consistently activated the phosphatidylinositol 3-kinase pathway. Furthermore, SBR serum markedly augmented rat intestinal epithelial cell growth, an effect that was abolished by EGFR inhibition.


CONCLUSIONS
SBR serum contains a factor or factors that stimulates proliferation of intestinal epithelial cells by an EGFR and phosphatidylinositol 3-kinase signaling mechanism. These data recapitulate in vivo studies supporting the hypothesis that EGFR is a central mediator of postresection intestinal adaptation. This in vitro model may provide a novel means to gain insight into the pathophysiology of intestinal adaptation.
Juno
Russell J
RJ
Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Department of Surgery, University of Cincinnati College of Medicine, Ohio 45229, USA.
Williams
Jodi L
JL
Knott
Andrew W
AW
Erwin
Christopher R
CR
O'brien
David P
DP
Warner
Brad W
BW
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D000077156:Gefitinib; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism*; D007421:Intestine, Small / Q000601:surgery*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
D001798:Blood Proteins; D004791:Enzyme Inhibitors; D011799:Quinazolines; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D000077156:Gefitinib