Spiny mice activate unique transcriptional programs after severe kidney injury regenerating organ function without fibrosis

Daryl M. Okamura, Chris M. Brewer, Paul Wakenight, Nadia Bahrami, Kristina Bernardi, Amy Tran, Jill Olson, Xiaogang Shi, Szu Ying Yeh, Adrian Piliponsky, Sarah J. Collins, Elizabeth D. Nguyen, Andrew E. Timms, James W. MacDonald, Theo K. Bammler, Branden R. Nelson, Kathleen J. Millen, David R. Beier, Mark W. Majesky

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Fibrosis-driven solid organ failure is an enormous burden on global health. Spiny mice (Acomys) are terrestrial mammals that can regenerate severe skin wounds without scars to avoid predation. Whether spiny mice also regenerate internal organ injuries is unknown. Here, we show that despite equivalent acute obstructive or ischemic kidney injury, spiny mice fully regenerate nephron structure and organ function without fibrosis, whereas C57Bl/6 or CD1 mice progress to complete organ failure with extensive renal fibrosis. Two mechanisms for vertebrate regeneration have been proposed that emphasize either extrinsic (pro-regenerative macrophages) or intrinsic (surviving cells of the organ itself) controls. Comparative transcriptome analysis revealed that the Acomys genome appears poised at the time of injury to initiate regeneration by surviving kidney cells, whereas macrophage accumulation was not detected until about day 7. Thus, we provide evidence for rapid activation of a gene expression signature for regenerative wound healing in the spiny mouse kidney.

Original languageEnglish
Article number103269
JournaliScience
Volume24
Issue number11
DOIs
StatePublished - 19 Nov 2021
Externally publishedYes

Keywords

  • Animal physiology
  • Developmental biology
  • Molecular biology

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