GUT 1998;43:64-70 ( July )

Reduced susceptibility of mice overexpressing transforming growth factor  to dextran sodium sulphate induced colitis

B Egger,^a H V Carey,^c F Procaccino,^a N-N Chai,^a E P Sandgren,^d J Lakshmanan,^a V S Buslon,^b S W French,^b M W Büchler,^e V E Eysselein^a

^a Inflammatory Bowel Disease Center, Harbor-UCLA Medical Center, Torrance, CA 90509, USA, ^b Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA, ^c Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA, ^d Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA, ^e Department of Visceral and Transplantation Surgery, University of Bern, CH-3010 Bern, Switzerland

Correspondence to: Dr V E Eysselein, Harbor-UCLA Medical Center, Division of Gastroenterology, 1124 West Carson Street, N-16, Torrance, CA 90502, USA.

Accepted for publication 4 February 1998

BackgroundTransforming growth factor  (TGF-) knockout mice have increased susceptibility to dextran sodium sulphate (DSS) induced colitis.
AimTo substantiate the findings that TGF- is a key mediator of colonic mucosal protection and/or repair mechanisms by evaluating the susceptibility of mice overexpressing TGF- to DSS induced colitis.
MethodsTGF- overexpression was induced in transgenic mice by ZnSO₄ administration in drinking water (TG+). Three groups were used as controls: one transgenic group without ZnSO₄ administration (TG), and two non-transgenic littermate groups receiving ZnSO₄ (Non-TG+) or only water (Non-TG). Acute colitis was induced in all groups by administration of DSS (5%, w/v) in drinking water for six days ad libitum.
ResultsAbout 35-39% of the entire colonic mucosa was destroyed in Non-TG, Non-TG+, and TG animals compared with 9% in TG+ mice. The crypt damage score was 18.7 (0.9), 18.2 (1.0), 18.9 (0.8), and 6.8 (1.5) (means (SEM)) in Non-TG, Non-TG+, TG, and TG+ mice respectively. Mucin and bromodeoxyuridine staining were markedly enhanced in colons of TG+ mice compared with controls, indicating increased mucosal protection and regeneration.
ConclusionsThe significantly reduced susceptibility of mice overexpressing TGF- to DSS further substantiates that endogenous TGF- is a pivotal mediator of protection and/or healing mechanisms in the colon.
(GUT 1998;43:64-70)

Keywords: transforming growth factor ;  epidermal growth factor;  dextran sodium sulphate;  colitis;  inflammatory bowel disease;  transgenic mice

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© 1998 by Gut
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