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

ABSTRACT

BACKGROUND & AIMS: There is indirect evidence that transforming growth factor alpha (TGF-alpha) is an important mediator of mucosal defense and repair. TGF-alpha knockout mice and TGF-alpha-deficient mice (wa-1) provide novel approaches to evaluate the role of TGF-alpha 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-alpha was also administered intraperitoneally to wa-1 mice to evaluate the effect of exogenous TGF-alpha 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-alpha application to wa-1 mice reduced the severity of mucosal injury by almost 70% compared with controls. CONCLUSIONS: The marked susceptibility of TGF-alpha knockout and wa-1 mice to DSS and the obvious amelioration of the colonic injury by exogenous TGF-alpha application in wa-1 mice suggest that TGF-alpha is a mediator of protection and/or healing mechanisms in the colon.