Reduction of Smad3 accelerates re-epithelialization in a murine model of colitis.
To determine the role of Smad3 in re-epithelialization and inflammation, experimental colitis was induced in Smad3 heterozygous mice and their wild-type littermates by single intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in ethanol. The area of epithelial deficiency was significantly reduced in the heterozygotes on the 4th-6th day after TNBS administration as compared to the controls although the number of inflammatory cells in the colonic mucosa in the heterozygotes and their wild-type littermates varied similarly throughout the course of colitis. Proliferation of the intestinal epithelium in the heterozygotes was significantly accelerated as compared to that in the wild-type controls on the 1st and 2nd days after TNBS administration. These results suggest that reduction of Smad3 significantly accelerates re-epithelialization of the intestinal mucosa without enhancing inflammation. Suppression of TGF-beta1 induction in the colonic mucosa of the heterozygotes may lead to a higher level of proliferation of intestinal epithelial cells.
Tokumasa
Atsuko
A
Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ward, Chiba-City 260-8670, Japan.
Katsuno
Tatsuro
T
Tanaga
Tsunemi S
TS
Yokote
Koutaro
K
Saito
Yasushi
Y
Suzuki
Yasuo
Y
D000818:Animals; D002455:Cell Division; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration / Q000502:physiology*; D012720:Severity of Illness Index; D051900:Smad3 Protein; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid; D014945:Wound Healing / Q000502:physiology*
D004268:DNA-Binding Proteins; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014302:Trinitrobenzenesulfonic Acid