Mice lacking transforming growth factor α have an increased susceptibility to dextran sulfate-induced colitis

Abstract

Background and Aims: There is indirect evidence that transforming growth factor α (TGF-α) is an important mediator of mucosal defense and repair. TGF-α knock-out mice and TGF-α-deficient mice (wa-1) provide novel approaches to evaluate the role of TGF-α in preserving the integrity of the colon. Methods: Colitis was induced by oral administration of dextran sodium sulfate (DSS, 5 g/dL) to knockout mice, their genetic controls (GC), wa-1 mice, and BALB/c mice. TGF-α was also administered intraperitoneally to wa- 1 mice to evaluate the effect of exogenous TGF-α in DSS colitis. Results: In response to DSS, nearly 60% of the entire colonic mucosa was destroyed in knockout and wa-1 mice, comPared with 22% in GC mice and 16% in BALB/c mice. Body weight loss was doubled in knockout (28%) and wa-1 mice (23%) compared with GC (11%) and Balb/c mice (12%), TGF-α application to wa-1 mice reduced the severity of mucosal injury by almost 70% compared with controls. Conclusions: The marked susceptibility of TGF-α knockout and wa-1 mice to DSS and the obvious amelioration of the colonic injury by exogenous TGF-α application in wa-1 mice suggest that TGF-α is a mediator of protection and/or healing mechanisms in the colon.