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Endocycle-related tubular cell hypertrophy and progenitor proliferation recover renal function after acute kidney injury

Acute kidney injury (AKI) is considered largely reversible based on the capacity of surviving tubular cells to dedifferentiate and replace lost cells via cell division. Here we show by tracking individual tubular cells in conditional Pax8/Confetti mice that kidney function is  recovered after AKI de...

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Detalles Bibliográficos
Autores principales: Lazzeri, Elena, Angelotti, Maria Lucia, Peired, Anna, Conte, Carolina, Marschner, Julian A., Maggi, Laura, Mazzinghi, Benedetta, Lombardi, Duccio, Melica, Maria Elena, Nardi, Sara, Ronconi, Elisa, Sisti, Alessandro, Antonelli, Giulia, Becherucci, Francesca, De Chiara, Letizia, Guevara, Ricardo Romero, Burger, Alexa, Schaefer, Beat, Annunziato, Francesco, Anders, Hans-Joachim, Lasagni, Laura, Romagnani, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890293/
https://www.ncbi.nlm.nih.gov/pubmed/29632300
http://dx.doi.org/10.1038/s41467-018-03753-4
Descripción
Sumario:Acute kidney injury (AKI) is considered largely reversible based on the capacity of surviving tubular cells to dedifferentiate and replace lost cells via cell division. Here we show by tracking individual tubular cells in conditional Pax8/Confetti mice that kidney function is  recovered after AKI despite substantial tubular cell loss. Cell cycle and ploidy analysis upon AKI in conditional Pax8/FUCCI2aR mice and human biopsies identify endocycle-mediated hypertrophy of tubular cells. By contrast, a small subset of Pax2+ tubular progenitors enriches via higher stress resistance and clonal expansion and regenerates necrotic tubule segments, a process that can be enhanced by suitable drugs. Thus,  renal functional recovery upon AKI involves remnant tubular cell hypertrophy via endocycle and limited progenitor-driven regeneration that can be pharmacologically enhanced.