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Differentiated kidney epithelial cells repair injured proximal tubule

Kusaba, Tetsuro ; Lalli, Matthew ; Kramann, Rafael ; Kobayashi, Akio ; Humphreys, Benjamin D.

Proceedings of the National Academy of Sciences - PNAS, 2014-01, Vol.111 (4), p.1527-1532 [Periódico revisado por pares]

United States: National Academy of Sciences

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  • Título:
    Differentiated kidney epithelial cells repair injured proximal tubule
  • Autor: Kusaba, Tetsuro ; Lalli, Matthew ; Kramann, Rafael ; Kobayashi, Akio ; Humphreys, Benjamin D.
  • Assuntos: Biological Sciences ; Cell Differentiation ; Cell growth ; Epithelial cells ; Epithelial Cells - cytology ; Humans ; Injuries ; Kidney - cytology ; Kidney cells ; Kidney cortex ; Kidney Tubules, Proximal - injuries ; Kidney Tubules, Proximal - metabolism ; Kidney Tubules, Proximal - pathology ; Kidneys ; Nephrons ; Physical trauma ; Progenitor cells ; Proximal tubules ; Recombination, Genetic ; Stem cells ; Vimentin
  • É parte de: Proceedings of the National Academy of Sciences - PNAS, 2014-01, Vol.111 (4), p.1527-1532
  • Notas: http://dx.doi.org/10.1073/pnas.1310653110
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    Author contributions: T.K. and B.D.H. designed research; T.K., M.L., and R.K. performed research; M.L., R.K., and A.K. contributed new reagents/analytic tools; T.K., R.K., and B.D.H. analyzed data; and T.K. and B.D.H. wrote the paper.
    Edited* by Brigid L. M. Hogan, Duke University Medical Center, Durham, NC, and approved September 10, 2013 (received for review June 10, 2013)
  • Descrição: Whether kidney proximal tubule harbors a scattered population of epithelial stem cells is a major unsolved question. Lineage-tracing studies, histologic characterization, and ex vivo functional analysis results conflict. To address this controversy, we analyzed the lineage and clonal behavior of fully differentiated proximal tubule epithelial cells after injury. A CreER ᵀ² cassette was knocked into the sodium-dependent inorganic phosphate transporter SLC34a1 locus, which is expressed only in differentiated proximal tubule. Tamoxifen-dependent recombination was absolutely specific to proximal tubule. Clonal analysis after injury and repair showed that the bulk of labeled cells proliferate after injury with increased clone size after severe compared with mild injury. Injury to labeled proximal tubule epithelia induced expression of CD24, CD133, vimentin, and kidney-injury molecule-1, markers of putative epithelial stem cells in the human kidney. Similar results were observed in cultured proximal tubules, in which labeled clones proliferated and expressed dedifferentiation and injury markers. When mice with completely labeled kidneys were subject to injury and repair there was no dilution of fate marker despite substantial proliferation, indicating that unlabeled progenitors do not contribute to kidney repair. During nephrogenesis and early kidney growth, single proximal tubule clones expanded, suggesting that differentiated cells also contribute to tubule elongation. These findings provide no evidence for an intratubular stem-cell population, but rather indicate that terminally differentiated epithelia reexpress apparent stem-cell markers during injury-induced dedifferentiation and repair.
  • Editor: United States: National Academy of Sciences
  • Idioma: Inglês
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