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Telomere shortening reduces regenerative capacity after acute kidney injury

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 t...

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Main Authors: Westhoff, Jens (Author) , Schildhorn, Carolin (Author) , Jacobi, Christoph (Author) , Hömme, Meike (Author) , Hartner, Andrea (Author) , Braun, Heidi M. (Author) , Kryzer, Christine (Author) , Wang, Chunfang (Author) , von Zglinicki, Thomas (Author) , Kränzlin, Bettina (Author) , Gretz, Norbert (Author) , Melk, Anette (Author)
Format: Article (Journal)
Language:English
Published: February 2010
In: Journal of the American Society of Nephrology
Year: 2010, Volume: 21, Issue: 2, Pages: 327-336
ISSN:1533-3450
DOI:10.1681/ASN.2009010072
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1681/ASN.2009010072
Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/jasn/fulltext/2010/02000/telomere_shortening_reduces_regenerative_capacity.18.aspx
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Author Notes:Jens H. Westhoff, Carolin Schildhorn, Christoph Jacobi, Meike Hömme, Andrea Hartner, Heidi Braun, Christine Kryzer, Chunfang Wang, Thomas von Zglinicki, Bettina Kränzlin, Norbert Gretz, and Anette Melk
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Summary: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.
Item Description:Gesehen am 29.11.2023
Physical Description:Online Resource
ISSN:1533-3450
DOI:10.1681/ASN.2009010072

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