Reduction of Smad3 accelerates re-epithelialization in a murine model of colitis

• Published in: Biochemical and biophysical research communications Vol. 317; no. 2; pp. 377 - 383
• Main Authors: Tokumasa, Atsuko, Katsuno, Tatsuro, Tanaga, Tsunemi S, Yokote, Koutaro, Saito, Yasushi, Suzuki, Yasuo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.04.2004
• Subjects: Animals; Cell Division; Colitis - chemically induced; Colitis - metabolism; Colitis - pathology; Disease Models, Animal; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; Experimental colitis; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - pathology; Intestinal Mucosa - drug effects; Intestinal Mucosa - growth & development; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Male; Mice; Mice, Inbred C57BL; Re-epithelialization; Regeneration - physiology; Severity of Illness Index; Smad3; Smad3 Protein; TGF-β; TNBS; Trans-Activators - deficiency; Trans-Activators - genetics; Transforming Growth Factor beta - metabolism; Trinitrobenzenesulfonic Acid; Wound Healing - physiology; Experimental colitis; TGF-β; Smad3; Re-epithelialization; TNBS
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.03.047

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-β1 induction in the colonic mucosa of the heterozygotes may lead to a higher level of proliferation of intestinal epithelial cells.