title: Telomere shortening reduces regenerative capacity after acute kidney injury.
abstract: Telomeres of most somatic cells progressively shorten, compromising the regenerative capacity of human tissues during aging and chronic diseases and after acute injury. Whether telomere shortening reduces renal regeneration after acute injury is unknown. Here, renal ischemia-reperfusion injury led to greater impairment of renal function and increased acute and chronic histopathologic damage in fourth-generation telomerase-deficient mice compared with both wild-type and first-generation telomerase-deficient mice. Critically short telomeres, increased expression of the cell-cycle inhibitor p21, and more apoptotic renal cells accompanied the pronounced damage in fourth-generation telomerase-deficient mice. These mice also demonstrated significantly reduced proliferative capacity in tubular, glomerular, and interstitial cells. These data suggest that critical telomere shortening in the kidney leads to increased senescence and apoptosis, thereby limiting regenerative capacity in response to injury.
authors: Children's Hospital, Medical School Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors: Jens H
authors: JH
authors: Westhoff
authors: Carolin
authors: C
authors: Schildhorn
authors: Christoph
authors: C
authors: Jacobi
authors: Meike
authors: M
authors: Hömme
authors: Andrea
authors: A
authors: Hartner
authors: Heidi
authors: H
authors: Braun
authors: Christine
authors: C
authors: Kryzer
authors: Chunfang
authors: C
authors: Wang
authors: Thomas
authors: T
authors: von Zglinicki
authors: Bettina
authors: B
authors: Kränzlin
authors: Norbert
authors: N
authors: Gretz
authors: Anette
authors: A
authors: Melk
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004195:Disease Models, Animal; D007668:Kidney / Q000473:pathology / Q000502:physiology* / Q000601:surgery; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009392:Nephrectomy; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; C422952:telomerase RNA; D055513:Connective Tissue Growth Factor; D012313:RNA; D019098:Telomerase