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

被引：190

作者：

Lazzeri, Elena ^{[1
,2
]}

Angelotti, Maria Lucia ^{[1
,2
]}

Peired, Anna ^{[1
,2
]}

Conte, Carolina ^{[1
,2
]}

Marschner, Julian A. ^{[3
]}

Maggi, Laura ^{[2
]}

Mazzinghi, Benedetta ^{[4
,5
]}

Lombardi, Duccio ^{[1
,2
]}

Melica, Maria Elena ^{[1
]}

Nardi, Sara ^{[1
,2
]}

Ronconi, Elisa ^{[1
,2
]}

Sisti, Alessandro ^{[1
,4
,5
]}

Antonelli, Giulia ^{[1
,2
]}

Becherucci, Francesca ^{[4
,5
]}

De Chiara, Letizia ^{[4
,5
]}

Guevara, Ricardo Romero ^{[1
,2
]}

Burger, Alexa ^{[6
]}

Schaefer, Beat ^{[7
,8
]}

Annunziato, Francesco ^{[2
]}

Anders, Hans-Joachim ^{[3
]}

Lasagni, Laura ^{[1
,2
]}

Romagnani, Paola ^{[1
,2
,4
,5
]}

机构：

[1] Univ Florence, Dept Clin & Expt Biomed Sci, Florence, Italy

[2] Excellence Ctr Res Transfer & High Educ Dev DE NO, Florence, Italy

[3] Klinikum LMU Munchen, Med Klin & Poliklin 4, Div Nephrol, Munich, Germany

[4] Nephrol Unit, Florence, Italy

[5] Meyer Childrens Univ Hosp, Florence, Italy

[6] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland

[7] Univ Childrens Hosp, Dept Oncol, Zurich, Switzerland

[8] Univ Childrens Hosp, Childrens Res Ctr, Zurich, Switzerland

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

欧洲研究理事会;

关键词：

ENHANCES RECOVERY; EPITHELIAL-CELLS; CYCLE ARREST; REPAIR; FIBROSIS; DISEASE; LINEAGE; PATHOPHYSIOLOGY; COMPETITION; INHIBITION;

D O I：

10.1038/s41467-018-03753-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：18

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