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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / pathology*
  • Acute Kidney Injury / physiopathology*
  • Adult Stem Cells / pathology
  • Animals
  • Cell Cycle
  • Cell Dedifferentiation
  • Cell Enlargement
  • Cell Lineage
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Female
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Kidney Tubules / drug effects
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • PAX2 Transcription Factor / metabolism
  • PAX8 Transcription Factor / metabolism
  • Ploidies
  • Regeneration / drug effects
  • Single-Cell Analysis


  • Histone Deacetylase Inhibitors
  • PAX2 Transcription Factor
  • PAX8 Transcription Factor
  • Pax2 protein, mouse
  • Pax8 protein, mouse