Tubular cell polyploidy protects from lethal acute kidney injury but promotes consequent chronic kidney disease.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 10 2022
04 10 2022
Historique:
received:
30
09
2021
accepted:
02
09
2022
entrez:
4
10
2022
pubmed:
5
10
2022
medline:
7
10
2022
Statut:
epublish
Résumé
Acute kidney injury (AKI) is frequent, often fatal and, for lack of specific therapies, can leave survivors with chronic kidney disease (CKD). We characterize the distribution of tubular cells (TC) undergoing polyploidy along AKI by DNA content analysis and single cell RNA-sequencing. Furthermore, we study the functional roles of polyploidization using transgenic models and drug interventions. We identify YAP1-driven TC polyploidization outside the site of injury as a rapid way to sustain residual kidney function early during AKI. This survival mechanism comes at the cost of senescence of polyploid TC promoting interstitial fibrosis and CKD in AKI survivors. However, targeting TC polyploidization after the early AKI phase can prevent AKI-CKD transition without influencing AKI lethality. Senolytic treatment prevents CKD by blocking repeated TC polyploidization cycles. These results revise the current pathophysiological concept of how the kidney responds to acute injury and identify a novel druggable target to improve prognosis in AKI survivors.
Identifiants
pubmed: 36195583
doi: 10.1038/s41467-022-33110-5
pii: 10.1038/s41467-022-33110-5
pmc: PMC9532438
doi:
Substances chimiques
Senotherapeutics
0
RNA
63231-63-0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5805Informations de copyright
© 2022. The Author(s).
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