Reduced susceptibility of mice overexpressing transforming growth factor alpha to dextran sodium sulphate induced colitis.
BACKGROUND
Transforming growth factor alpha (TGF-alpha) knockout mice have increased susceptibility to dextran sodium sulphate (DSS) induced colitis.


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


METHODS
TGF-alpha 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 and 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-alpha to DSS further substantiates that endogenous TGF-alpha is a pivotal mediator of protection and/or healing mechanisms in the colon.
Inflammatory Bowel Disease Center, Harbor-UCLA Medical Center, Torrance 90509, USA.
B
B
Egger
H V
HV
Carey
F
F
Procaccino
N N
NN
Chai
E P
EP
Sandgren
J
J
Lakshmanan
V S
VS
Buslon
S W
SW
French
M W
MW
Büchler
V E
VE
Eysselein
D000208:Acute Disease; D000818:Animals; D001835:Body Weight; D002455:Cell Division; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D004198:Disease Susceptibility; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011863:Radioimmunoassay; D018709:Statistics, Nonparametric; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000502:physiology*; D015032:Zinc / Q000008:administration & dosage
D016211:Transforming Growth Factor alpha; D016264:Dextran Sulfate; D015032:Zinc