Intrinsic Epithelial Cells Repair the Kidney after Injury
Open accessAbstract
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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β-gal-positive epithelial cells have robust self-renewal ability.
“these cells have robust self-renewal ability.61”
From Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice (2020) · cites this paper as [61]
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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.
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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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