Intestinal adaptation occurs independent of transforming growth factor- alpha

Background/Purpose: Signal transduction via the epidermal growth factor receptor (EGFR) is critical for intestinal adaptation after massive small bowel resection (SBR). Although it has been assumed that the major ligand for the EGFR during adaptation is EGF, the role for transforming growth factor-α (TGF-α), another major ligand for the EGFR is unknown. The purpose of this study was to test the hypothesis that TGF-α is an important ligand for the EGFR during intestinal adaptation. Methods: Wild-type mice (C57BI/6) underwent a 50% proximal SBR or sham operation (bowel transection or reanastomosis) and were then assigned randomly to receive either intraperitoneal TGF-α or placebo. In a separate experiment, SBR or sham operations were performed in mice lacking TGF-α (Waved-1). After 3 days, adaptation was measured in the ileum. Results: Exogenous TGF-α 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-α as shown by increased ileal wet weight, protein and DNA content, proliferation, villus height, and crypt depth. Conclusions: Although exogenous TGF-α enhanced adaptation after massive SBR, adaptation was preserved in TGF-α-absent mice. These results refute TGF-α as an essential ligand for EGFR signaling during intestinal adaptation. Copyright (C) 2000 by W.B. Saunders Company.