Altered mRNA expression of telomere binding proteins (TPP1, POT1, RAP1, TRF1 and TRF2) in ulcerative colitis and Crohn's disease

作者：Da Silva Nancy; Arasaradnam Ramesh; Getliffe Katherine; Sung Edward; Oo Ye; Nwokolo Chuka^*

来源：Digestive and Liver Disease, 2010, 42(8): 544-548.

DOI：10.1016/j.dld.2009.12.005

• Crohn's disease
• Peripheral blood mononuclear cells
• Telomere binding proteins
• Ulcerative colitis

Aims: To determine mRNA expression of telomeric binding proteins in inflammatory bowel disease (IBD), and to note any effects of pharmacotherapy on telomere binding protein expression.
Methods: Peripheral blood mononuclear cells (PBMC) obtained from 31 IBD patients and 13 controls were activated with phytohaemagglutinin and purified to yield activated (CD25+)T lymphocytes. TPP1, POT1, RAP1,TRF1 and TRF2 mRNA expression in PBMC and activated T lymphocytes was measured with RT-PCR. Results: In activated (CD25+) T lymphocytes, mean TRF2 mRNA levels were lower in both UC (6.6 vs 10, p = 0.004) and CD subjects (6.9 vs 10; p = 0.004). Similarly, in activated (CD25+) T lymphocytes mean RAP1 mRNA expression was significantly lower in UC subjects (4.5 vs 9.8, p = 0.029) but not in CD subjects. In resting PBMC, mean TRF1 mRNA levels were lower in both UC (2.6 vs 3.5; p = 0.008) and CD subjects (1.0 vs 3.5; p = 0.04). No difference in PBMC and activated (CD25+) T lymphocytes mRNA levels of TPP1 and POT1 were noted in either UC or CD subjects. An association with 5-aminosalicylate therapy (R(2) =0.4) was only detected with RAP1 mRNA expression. TRF2 mRNA expression was inversely associated with disease duration only in UC subjects (p = 0.05; R(2) = 0.6).
Conclusions: The downregulation of TRF2 and RAP1 mRNA expression in CD25+ T-lymphocytes in IBD suggests that these telomere binding proteins play a role in telomere regulation and may contribute to the telomeric fusions and chromosomal abnormalities observed in UC. These findings may also indicate a systemic process of telomere uncapping which could represent a biomarker for IBD associated cancer risk.

• 出版日期2010-8