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Inflammation and inflammatory bowel disease
Reduced susceptibility of mice overexpressing transforming growth factor α to dextran sodium sulphate induced colitis
  1. B Eggera,
  2. H V Careyc,
  3. F Procaccinoa,
  4. N-N Chaia,
  5. E P Sandgrend,
  6. J Lakshmanana,
  7. V S Buslonb,
  8. S W Frenchb,
  9. M W Büchlere,
  10. V E Eysseleina
  1. aInflammatory Bowel Disease Center, Harbor-UCLA Medical Center, Torrance, CA 90509, USA, bDepartment of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA, cDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA, dDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA, eDepartment of Visceral and Transplantation Surgery, University of Bern, CH-3010 Bern, Switzerland
  1. Dr V E Eysselein, Harbor-UCLA Medical Center, Division of Gastroenterology, 1124 West Carson Street, N-16, Torrance, CA 90502, USA.

Abstract

Background—Transforming growth factor α (TGF-α) knockout mice have increased susceptibility to dextran sodium sulphate (DSS) induced colitis.

Aim—To substantiate the findings that TGF-α is a key mediator of colonic mucosal protection and/or repair mechanisms by evaluating the susceptibility of mice overexpressing TGF-α to DSS induced colitis.

Methods—TGF-α overexpression was induced in transgenic mice by ZnSO4administration 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.

Results—About 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.

Conclusions—The significantly reduced susceptibility of mice overexpressing TGF-α to DSS further substantiates that endogenous TGF-α is a pivotal mediator of protection and/or healing mechanisms in the colon.

  • transforming growth factor α
  • epidermal growth factor
  • dextran sodium sulphate
  • colitis
  • inflammatory bowel disease
  • transgenic mice

https://doi.org/10.1136/gut.43.1.64

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