Press Release

Importance of telomere shortening in the pathogenesis of ulcerative colitis: A new treatment from the aspect of telomeres in intestinal epithelial cells

Abstract

Background and Aims
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with frequent relapses. Telomere shortening in intestinal epithelial cells has been reported in severe or longstanding cases. However, its influence on UC pathogenesis remains unelucidated. To this end, we evaluated telomere shortening using a long-term organoid inflammation model that we had originally established.

Methods
A UC model using human colon organoids was established to assess telomere changes chronologically. MST-312 was used for the telomerase inhibition assay. The potential of telomerase activators as a novel UC treatment was evaluated with an in vitro model, including microarray analysis, and histologic changes were assessed using xenotransplantation into mouse colonic mucosa.

Results
Our UC model reproduced telomere shortening in vitro, which was induced by the continuous suppression of telomerase activity via P53. MST-312-based analysis revealed that telomere shortening was involved in the pathogenesis of UC. Madecassoside (MD) improved the telomere length of the UC model and UC patient-derived organoids, which further promoted cell proliferation in vitro and improved the graft take-rate of xenotransplantation. Moreover, histologic analysis revealed that MD induced normal crypt structure with abundant goblet cells.

Conclusions
This study is the first to reveal the mechanism and importance of telomere shortening in the pathogenesis of UC. MD could be a novel candidate for UC treatment beyond endoscopic mucosal healing.

Journal Article

JOURNALJournal of Crohn’s and Colitis

TITLE:Importance of telomere shortening in the pathogenesis of ulcerative colitis: A new treatment from the aspect of telomeres in intestinal epithelial cells

DOIhttps://doi.org/10.1093/ecco-jcc/jjab115

Correspondence to

Kiichiro Tsuchiya,MD, PhD, Adjunct Lecturer

Department of Gastroenterology and Hepatology, 
Graduate School of Medical and Dental Sciences,
Tokyo Medical and Dental University (TMDU)
E-mail:kii.gast (at) tmd.ac.jp

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