TEMPORAL EXPRESSION OF TREFOIL PEPTIDES IN THE TGF-ALPHA KNOCKOUT MOUSE AFTER GASTRIC-ULCERATION

Trefoil peptides are gut peptides that have been implicated in the rep air of the gastric mucosa after injury. Previous studies suggest that epidermal growth factor (EGF) receptor ligands may induce the expressi on of trefoil peptides. Because transforming growth factor-alpha (TGF- alpha) is a major EGF receptor ligand in the gut, we tested the hypoth esis that mice with a TGF-alpha null mutation (knockout) would have re duced trefoil peptide expression compared with wild-type controls afte r gastric ulceration. The rate of macroscopic ulcer healing was the sa me in knockout and wild-type mice. Spasmolytic polypeptide (SP) and in testinal trefoil factor (ITF) expression were quantified in tissue and gastric lavage. SP and ITF levels in tissue fell within 48 h of ulcer ation (P < 0.05), but secretion into gastric juice was unchanged. ITF peptide expression was increased (as was SP expression) in wild-type b ut not knockout mice 42 and 72 days after injury (P < 0.05). The induc tion of SP and ITF expression in the latter stages of injury repair ha s a TGF-alpha-dependent component and suggests a role for these peptid es in gastric differentiation and cell positioning.