Deficiency of colonic telomerase in ulcerative colitis

Abstract

Objective: GI epithelial cells express telomerase, a ribonucleoprotein that prevents telomeric shortening in proliferating cells. Telomerase levels are high in cancer, but little is known about telomerase expression in other diseases. We, therefore, designed experiments to determine telomerase expression in different colonic segments and to compare this with corresponding segments in patients with ulcerative colitis. Colorectal cancers and adenomatous polyps were included as disease controls.

Methods: In total, telomerase expression was determined in colonic tissues obtained from 62 patients. Twenty-five patients had ulcerative colitis, 21 had normal colons, 11 had colorectal cancer, and nine had adenomatous polyps. Endoscopic biopsies were collected prospectively at colonoscopy, processed for telomerase assays (Telomeric Repeat Amplification Protocol), hematoxylin and eosin staining, and scored for inflammation.

Results: Telomerase activity is expressed in arbitrary units (median 95% confidence interval). In the normal colon, telomerase activity in the cecum, transverse, sigmoid, and rectum was 255 (171-449), 707 (374-895), 561 (468-1426), and 563 (402-846), respectively. Telomerase was higher in the distal three segments when compared with the cecum (p = 0.005). In ulcerative colitis, there was a marked decrease in telomerase activity in the cecum 152 (59-272), p = 0.04, transverse 180 (129-365), p < 0.001, sigmoid 352 (114-464), p = 0.005, and rectum 180 (70-337), p = 0.001 when compared with normals. Telomerase activity correlated negatively with inflammation (r = -0.32, p = 0.001) and was also decreased in microscopically normal areas. Cancers expressed high levels of telomerase.

Conclusions: Colonic mucosal expression of telomerase is reduced in ulcerative colitis. Levels are low even in microscopically normal mucosa, suggesting that telomerase deficiency may contribute to the pathogenesis of the disease.