Regeneration of the Exocrine Pancreas Is Delayed in Telomere-Dysfunctional Mice
Open Access
- 22 February 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (2), e17122
- https://doi.org/10.1371/journal.pone.0017122
Abstract
Telomere shortening is a cell-intrinsic mechanism that limits cell proliferation by induction of DNA damage responses resulting either in apoptosis or cellular senescence. Shortening of telomeres has been shown to occur during human aging and in chronic diseases that accelerate cell turnover, such as chronic hepatitis. Telomere shortening can limit organ homeostasis and regeneration in response to injury. Whether the same holds true for pancreas regeneration in response to injury is not known. In the present study, pancreatic regeneration after acute cerulein-induced pancreatitis was studied in late generation telomerase knockout mice with short telomeres compared to telomerase wild-type mice with long telomeres. Late generation telomerase knockout mice exhibited impaired exocrine pancreatic regeneration after acute pancreatitis as seen by persistence of metaplastic acinar cells and markedly reduced proliferation. The expression levels of p53 and p21 were not significantly increased in regenerating pancreas of late generation telomerase knockout mice compared to wild-type mice. Our results indicate that pancreatic regeneration is limited in the context of telomere dysfunction without evidence for p53 checkpoint activation.Keywords
This publication has 26 references indexed in Scilit:
- Chronic Pancreatitis: Challenges and Advances in Pathogenesis, Genetics, Diagnosis, and TherapyGastroenterology, 2007
- Telomerase Deletion Limits Progression of p53-Mutant Hepatocellular Carcinoma With Short Telomeres in Chronic Liver DiseaseGastroenterology, 2007
- Telomerase Mutations in Families with Idiopathic Pulmonary FibrosisNew England Journal of Medicine, 2007
- Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formationNature Genetics, 2006
- Telomere shortening with aging in the human pancreasExperimental Gerontology, 2006
- Gene Expression Profile at the G1/S Transition of Liver Regeneration after Partial Hepatectomy in MiceCell Cycle, 2004
- Telomere end-replication problem and cell agingJournal of Molecular Biology, 1992
- Growing Pancreatic Acinar Cells (Postpancreatitis and Fetal) Express a Ductal AntigenPancreas, 1990
- Tubular Complexes in Cerulein-and Oleic Acid-Induced Pancreatitis in RatsPancreas, 1987
- Time Course and Cellular Source of Pancreatic Regeneration Following Acute Pancreatitis in the RatPancreas, 1986