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Nat Commun. 2018 Apr 9;9(1):1344. doi: 10.1038/s41467-018-03753-4.

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

Author information

1
Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy.
2
Excellence Centre for Research, Transfer and High Education for the development of DE NOVO Therapies (DENOTHE), Florence, Italy.
3
Division of Nephrology, Medizinische Klinik and Poliklinik IV, Klinikum der LMU München, Munich, Germany.
4
Nephrology Unit and Meyer Children's University Hospital, Florence, Italy.
5
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
6
Department of Oncology and Children's Research Center, University Children's Hospital, Zurich, Switzerland.
7
Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy. paola.romagnani@unifi.it.
8
Excellence Centre for Research, Transfer and High Education for the development of DE NOVO Therapies (DENOTHE), Florence, Italy. paola.romagnani@unifi.it.
9
Nephrology Unit and Meyer Children's University Hospital, Florence, Italy. paola.romagnani@unifi.it.

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.

PMID:
29632300
PMCID:
PMC5890293
DOI:
10.1038/s41467-018-03753-4
[Indexed for MEDLINE]
Free PMC Article

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