原创力文档regeneration of the exocrine pancreas is delayed in telomere-dysfunctional mice再生telomere-dysfunctional外分泌胰腺被延迟的老鼠.pdfVIP
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regeneration of the exocrine pancreas is delayed in telomere-dysfunctional mice再生telomere-dysfunctional外分泌胰腺被延迟的老鼠
Regeneration of the Exocrine Pancreas Is Delayed in
Telomere-Dysfunctional Mice
1,2 2 1 1,3
Guido von Figura , Martin Wagner , Kodandaramireddy Nalapareddy , Daniel Hartmann , Alexander
1,2 1 1 2 1
Kleger , Luis Miguel Guachalla , Harshvardhan Rolyan , Guido Adler , Karl Lenhard Rudolph *
1 Institute of Molecular Medicine and Max-Planck-Research-Group on Stem Cell Aging, University of Ulm, Ulm, Germany, 2 Department of Internal Medicine I, University of
Ulm, Ulm, Germany, 3 Department of Surgery, Technical University of Munich, Munich, Germany
Abstract
Introduction: 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.
Methods: 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.
Results: Late generation telomerase knockout mice exhibited impaired exocrine pancreatic regeneration after acute
pancreatitis as seen by persistence of metaplastic acinar cells and markedly reduced proliferatio
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