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

Elena Lazzeri, Maria Lucia Angelotti, Anna Peired, Carolina Conte, Julian A. Marschner, Laura Maggi, Benedetta Mazzinghi, Duccio Lombardi, Maria Elena Melica, Sara Nardi, Elisa Ronconi, Alessandro Sisti, Giulia Antonelli, Francesca Becherucci, Letizia Chiara, Ricardo Romero Guevara, Alexa Burger, Beat Schaefer, Francesco Annunziato, Hans-Joachim Anders, Laura Lasagni and Paola Romagnani ()
Additional contact information
Elena Lazzeri: University of Florence
Maria Lucia Angelotti: University of Florence
Anna Peired: University of Florence
Carolina Conte: University of Florence
Julian A. Marschner: Klinikum der LMU München
Laura Maggi: Transfer and High Education for the development of DE NOVO Therapies (DENOTHE)
Benedetta Mazzinghi: Nephrology Unit and Meyer Children’s University Hospital
Duccio Lombardi: University of Florence
Maria Elena Melica: University of Florence
Sara Nardi: University of Florence
Elisa Ronconi: University of Florence
Alessandro Sisti: University of Florence
Giulia Antonelli: University of Florence
Francesca Becherucci: Nephrology Unit and Meyer Children’s University Hospital
Letizia Chiara: Nephrology Unit and Meyer Children’s University Hospital
Ricardo Romero Guevara: University of Florence
Alexa Burger: University of Zurich
Beat Schaefer: University Children’s Hospital
Francesco Annunziato: Transfer and High Education for the development of DE NOVO Therapies (DENOTHE)
Hans-Joachim Anders: Klinikum der LMU München
Laura Lasagni: University of Florence
Paola Romagnani: University of Florence

Nature Communications, 2018, vol. 9, issue 1, 1-18

Abstract: Abstract 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03753-4

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DOI: 10.1038/s41467-018-03753-4

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