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Telomere shortening reduces regenerative capacity after acute kidney injury

Lookup NU author(s): Chunfang Wang

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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 firstgeneration telomerase-deficient mice. Critically short telomeres, increased expression of the cellcycle inhibitor p21, and more apoptotic renal cells accompanied the pronounced damage in fourthgeneration 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. Copyright © 2010 by the American Society of Nephrology.

Publication metadata

Author(s): Westhoff J, Schildhorn C, Jacobi C, Hömme M, Hartner A, Braun H, Kryzer C, Wang C, Zglinicki T, Kränzlin B, Gretz N, Melk A

Publication type: Article

Publication status: Published

Journal: Journal of the American Society of Nephrology

Year: 2010

Volume: 21

Issue: 2

Pages: 327-336

ISSN (print): 1046-6673

ISSN (electronic): 1533-3450

Publisher: American Society of Nephrology

URL: http://dx.doi.org/10.1681/ASN.2009010072

DOI: 10.1681/ASN.2009010072

PubMed id: 19959722

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