Pietro Invernizzi1, Francesca Bernuzzi1, Ana Lleo1, Vanila Pozzoli2, Monica Bignotto3, Paola Zermiani2, Andrea Crosignani2, Pier Maria Battezzati2, Massimo Zuin2, Mauro Podda1, Chiara Raggi4. 1. Liver Unit and Center for Autoimmune Liver Diseases Humanitas Clinical and Research Center, Rozzano, Italy. 2. Gastroenterology and Liver Unit, San Paolo Hospital Medical School, University of Milan, Milan, Italy. 3. Gastroenterology and Liver Unit, San Paolo Hospital Medical School, University of Milan, Milan, Italy; Department of Human Morphology and Biomedical Sciences, University of Milan, Italy. 4. Liver Unit and Center for Autoimmune Liver Diseases Humanitas Clinical and Research Center, Rozzano, Italy. Electronic address: chiara.raggi@humanitasresearch.it.
Abstract
BACKGROUND: Chromosomal instability in peripheral blood mononuclear cells has a role in the onset of primary biliary cirrhosis. We hypothesized that patients with primary biliary cirrhosis may harbour telomere dysfunction, with consequent chromosomal instability and cellular senescence. AIM: To evaluate the clinical significance of telomerase activity and telomere length in peripheral blood mononuclear cells from patients with primary biliary cirrhosis. STUDY DESIGN: In this population-based case control study, 48 women with primary biliary cirrhosis (25 with cirrhosis), 12 with chronic hepatitis C matched by age and severity of disease, and 55 age-matched healthy women were identified. Mononuclear cells from the peripheral blood of patients and controls were isolated. Telomere length and telomerase activity were measured. RESULTS: Telomere length and telomerase activity did not differ between cases (5.9 ± 1.5 kb) and controls (6.2 ± 1.4 kb, pc=0.164). Telomere shortening and advanced-stage disease strongly correlated with telomerase activity. Patients with advanced disease retained significantly less telomerase activity than those with early-stage disease (0.6 ± 0.9 OD vs. 1.5 ± 3.7 OD, p=0.03). Telomere loss correlated with age, suggesting premature cellular ageing in patients with primary biliary cirrhosis. CONCLUSION: Our data strongly support the telomere hypothesis of human cirrhosis, indicating that telomere shortening and telomerase activity represent a molecular mechanism in the evolution of human cirrhosis in a selected population of patients.
BACKGROUND: Chromosomal instability in peripheral blood mononuclear cells has a role in the onset of primary biliary cirrhosis. We hypothesized that patients with primary biliary cirrhosis may harbour telomere dysfunction, with consequent chromosomal instability and cellular senescence. AIM: To evaluate the clinical significance of telomerase activity and telomere length in peripheral blood mononuclear cells from patients with primary biliary cirrhosis. STUDY DESIGN: In this population-based case control study, 48 women with primary biliary cirrhosis (25 with cirrhosis), 12 with chronic hepatitis C matched by age and severity of disease, and 55 age-matched healthy women were identified. Mononuclear cells from the peripheral blood of patients and controls were isolated. Telomere length and telomerase activity were measured. RESULTS: Telomere length and telomerase activity did not differ between cases (5.9 ± 1.5 kb) and controls (6.2 ± 1.4 kb, pc=0.164). Telomere shortening and advanced-stage disease strongly correlated with telomerase activity. Patients with advanced disease retained significantly less telomerase activity than those with early-stage disease (0.6 ± 0.9 OD vs. 1.5 ± 3.7 OD, p=0.03). Telomere loss correlated with age, suggesting premature cellular ageing in patients with primary biliary cirrhosis. CONCLUSION: Our data strongly support the telomere hypothesis of humancirrhosis, indicating that telomere shortening and telomerase activity represent a molecular mechanism in the evolution of humancirrhosis in a selected population of patients.
Authors: Karin de Punder; Christine Heim; Ingo Przesdzing; Pathik D Wadhwa; Sonja Entringer Journal: Philos Trans R Soc Lond B Biol Sci Date: 2018-03-05 Impact factor: 6.237