Cited by 868Acute Kidney Injury ResearchRenal and related cancersLiver physiology and pathology

Intrinsic Epithelial Cells Repair the Kidney after Injury

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Humphreys, Benjamin D., Valerius, M. Todd, Kobayashi, Akio, Mugford, Joshua W., Soeung, Savuth, Duffield, Jeremy S., McMahon, Andrew P., Bonventre, Joseph V.·2008·Cell Stem Cell

Abstract

Understanding the mechanisms of nephron repair is critical for the design of new therapeutic approaches to treat kidney disease. The kidney can repair after even a severe insult, but whether adult stem or progenitor cells contribute to epithelial renewal after injury and the cellular origin of regenerating cells remain controversial. Using genetic fate-mapping techniques, we generated transgenic mice in which 94%-95% of tubular epithelial cells, but no interstitial cells, were labeled with either beta-galactosidase (lacZ) or red fluorescent protein (RFP). Two days after ischemia-reperfusion injury (IRI), 50.5% of outer medullary epithelial cells coexpress Ki67 and RFP, indicating that differentiated epithelial cells that survived injury undergo proliferative expansion. After repair was complete, 66.9% of epithelial cells had incorporated BrdU, compared to only 3.5% of cells in the uninjured kidney. Despite this extensive cell proliferation, no dilution of either cell-fate marker was observed after repair. These results indicate that regeneration by surviving tubular epithelial cells is the predominant mechanism of repair after ischemic tubular injury in the adult mammalian kidney.

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Crossref · 10.1016/j.stem.2008.01.014

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Authors
Humphreys, B. D., Valerius, M. T., Kobayashi, A., Mugford, J. W., Soeung, S., Duffield, J. S., McMahon, A. P., & Bonventre, J. V.
Affiliations
  • Brigham and Women's Hospital (US)
  • Harvard University (US)
Corresponding author
  • Humphreys, Benjamin D.
  • McMahon, Andrew P.
  • Bonventre, Joseph V.
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2008-03
Volume
2
Issue
3
Pages
284-291
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W2018091219
Cited by
868
References
31
Citations by year
2026: 18 · 2025: 23 · 2024: 45 · 2023: 30 · 2022: 46 · 2021: 49 · 2020: 43 · 2019: 47 · 2018: 40 · 2017: 37 · 2016: 59 · 2015: 64 · 2014: 67 · 2013: 63 · 2012: 58
FWCI
47.71
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases ([DK054364, DK-39773, K08DK073628, DK73299, DK73628, K08DK073299)
  • National Institute of Neurological Disorders and Stroke (R37NS033642)
Topics
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
kidney regeneration, tubular epithelial cells, ischemia-reperfusion injury, cell proliferation, cell fate mapping, transgenic mice, stem/progenitor cells
MeSH terms
Animals, Epithelial Cells, Kidney Diseases, Kidney Tubules, Mice, Transgenic, Regeneration, Time Factors, Reperfusion Injury, Cell Proliferation, Mice, Adult Stem Cells

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