Intestinal adaptation occurs independent of transforming growth factor-alpha

Background/Purpose: Signal transduction via the epidermal growth factor rec eptor (EGFR) is critical for intestinal adaptation after massive small bowe l resection (SBR). Although it has been assumed that the major ligand for t he EGFR during adaptation is EGF, the role for transforming growth factor-a lpha (TGF-alpha), another major ligand for the EGFR is unknown. The purpose of this study was to test the hypothesis that TG F-alpha is an important l igand for the EGFR during intestinal adaptation. Methods: Wild-type mice (C57Bl/6) underwent a 50% proximal SBR or sham oper ation (bowel transection or reanastomosis) and were then assigned randomly to receive either intraperitoneal TGF-alpha or placebo. In a separate exper iment, SBR or sham operations were performed in mice lacking TGF-alpha (Wav ed-1). After 3 days, adaptation was measured in the ileum, Results: Exogeno us TGF-alpha enhanced intestinal adaptation in the wild-type mice after SBR as shown by increased ileal wet weight and DNA content. Normal adaptation occurred in the mice lacking TGF-alpha as shown by increased ileal wet weig ht, protein and DNA content, proliferation, villus height, and crypt depth. Conclusions: Although exogenous TGF-alpha enhanced adaptation after massive SBR, adaptation was preserved in TGF-alpha-absent mice. These results refu te TGF-alpha as an essential ligand for EGFR signaling during intestinal ad aptation. J Pediatr Surg 35:365-370. Copyright (C) 2000 by W.B. Saunders Co mpany.