Projects per year
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.
- Biomarkers, Tumor
- Chromosomal Instability
- Colitis, Ulcerative
- Colonic Neoplasms
- Crohn Disease
- Leukocytes, Mononuclear
- Lymphocyte Activation
- Middle Aged
- RNA, Messenger
- Reverse Transcriptase Polymerase Chain Reaction
- Telomere-Binding Proteins
- Telomeric Repeat Binding Protein 1
- Telomeric Repeat Binding Protein 2
FingerprintDive into the research topics of 'Altered mRNA expression of telomere binding proteins (TPP1, POT1, RAP1, TRF1 and TRF2) in ulcerative colitis and Crohn's disease'. Together they form a unique fingerprint.
- 1 Finished
2/10/06 → 30/09/09
Project: Research Councils