Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration

B Smeets; P Boor; H Dijkman; SV Sharma; P Jirak; F Mooren; K Berger; J Bornemann; IH Gelman; J Floege; der Vlag J van; JFM Wetzels; MJ Moeller

doi:10.1002/path.4125

Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration

B Smeets, P Boor, H Dijkman, SV Sharma, P Jirak, F Mooren, K Berger, J Bornemann, IH Gelman, J Floege, der Vlag J van, JFM Wetzels, MJ Moeller

School of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

AbstractRegeneration of injured tubular cells occurs after acute tubular necrosis primarily from intrinsic renal cells. This may occur from a pre‐existing intratubular stem/progenitor cell population or from any surviving proximal tubular cell. In this study, we characterize a CD24‐, CD133‐, and vimentin‐positive subpopulation of cells scattered throughout the proximal tubule in normal human kidney. Compared to adjacent ‘normal’ proximal tubular cells, these CD24‐positive cells contained less cytoplasm, fewer mitochondria, and no brush border. In addition, 49 marker proteins are described that are expressed within the proximal tubules in a similar scattered pattern. For eight of these markers, we confirmed co‐localization with CD24. In human biopsies of patients with acute tubular necrosis (ATN), the number of CD24‐positive tubular cells was increased. In both normal human kidneys and the ATN biopsies, around 85% of proliferating cells were CD24‐positive – indicating that this cell population participates in tubular regeneration. In healthy rat kidneys, the novel cell subpopulation was absent. However, upon unilateral ureteral obstruction (UUO), the novel cell population was detected in significant amounts in the injured kidney. In summary, in human renal biopsies, the CD24‐positive cells represent tubular cells with a deviant phenotype, characterized by a distinct morphology and marker expression. After acute tubular injury, these cells become more numerous. In healthy rat kidneys, these cells are not detectable, whereas after UUO, they appeared de novo – arguing against the notion that these cells represent a pre‐existing progenitor cell population. Our data indicate rather that these cells represent transiently dedifferentiated tubular cells involved in regeneration. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Original language	English
Pages (from-to)	645-659
Number of pages	0
Journal	The Journal of Pathology
Volume	229
Issue number	5
Early online date	13 Mar 2013
DOIs	https://doi.org/10.1002/path.4125
Publication status	Published - Apr 2013

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Smeets, B., Boor, P., Dijkman, H., Sharma, SV., Jirak, P., Mooren, F., Berger, K., Bornemann, J., Gelman, IH., Floege, J., van, D. V. J., Wetzels, JFM., & Moeller, MJ. (2013). Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration. The Journal of Pathology, 229(5), 645-659. https://doi.org/10.1002/path.4125

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title = "Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration",

abstract = "AbstractRegeneration of injured tubular cells occurs after acute tubular necrosis primarily from intrinsic renal cells. This may occur from a pre‐existing intratubular stem/progenitor cell population or from any surviving proximal tubular cell. In this study, we characterize a CD24‐, CD133‐, and vimentin‐positive subpopulation of cells scattered throughout the proximal tubule in normal human kidney. Compared to adjacent {\textquoteleft}normal{\textquoteright} proximal tubular cells, these CD24‐positive cells contained less cytoplasm, fewer mitochondria, and no brush border. In addition, 49 marker proteins are described that are expressed within the proximal tubules in a similar scattered pattern. For eight of these markers, we confirmed co‐localization with CD24. In human biopsies of patients with acute tubular necrosis (ATN), the number of CD24‐positive tubular cells was increased. In both normal human kidneys and the ATN biopsies, around 85% of proliferating cells were CD24‐positive – indicating that this cell population participates in tubular regeneration. In healthy rat kidneys, the novel cell subpopulation was absent. However, upon unilateral ureteral obstruction (UUO), the novel cell population was detected in significant amounts in the injured kidney. In summary, in human renal biopsies, the CD24‐positive cells represent tubular cells with a deviant phenotype, characterized by a distinct morphology and marker expression. After acute tubular injury, these cells become more numerous. In healthy rat kidneys, these cells are not detectable, whereas after UUO, they appeared de novo – arguing against the notion that these cells represent a pre‐existing progenitor cell population. Our data indicate rather that these cells represent transiently dedifferentiated tubular cells involved in regeneration. Copyright {\textcopyright} 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.",

author = "B Smeets and P Boor and H Dijkman and SV Sharma and P Jirak and F Mooren and K Berger and J Bornemann and IH Gelman and J Floege and van, {der Vlag J} and JFM Wetzels and MJ Moeller",

year = "2013",

month = apr,

doi = "10.1002/path.4125",

language = "English",

volume = "229",

pages = "645--659",

journal = "The Journal of Pathology",

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TY - JOUR

T1 - Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration

AU - Smeets, B

AU - Boor, P

AU - Dijkman, H

AU - Sharma, SV

AU - Jirak, P

AU - Mooren, F

AU - Berger, K

AU - Bornemann, J

AU - Gelman, IH

AU - Floege, J

AU - van, der Vlag J

AU - Wetzels, JFM

AU - Moeller, MJ

PY - 2013/4

Y1 - 2013/4

N2 - AbstractRegeneration of injured tubular cells occurs after acute tubular necrosis primarily from intrinsic renal cells. This may occur from a pre‐existing intratubular stem/progenitor cell population or from any surviving proximal tubular cell. In this study, we characterize a CD24‐, CD133‐, and vimentin‐positive subpopulation of cells scattered throughout the proximal tubule in normal human kidney. Compared to adjacent ‘normal’ proximal tubular cells, these CD24‐positive cells contained less cytoplasm, fewer mitochondria, and no brush border. In addition, 49 marker proteins are described that are expressed within the proximal tubules in a similar scattered pattern. For eight of these markers, we confirmed co‐localization with CD24. In human biopsies of patients with acute tubular necrosis (ATN), the number of CD24‐positive tubular cells was increased. In both normal human kidneys and the ATN biopsies, around 85% of proliferating cells were CD24‐positive – indicating that this cell population participates in tubular regeneration. In healthy rat kidneys, the novel cell subpopulation was absent. However, upon unilateral ureteral obstruction (UUO), the novel cell population was detected in significant amounts in the injured kidney. In summary, in human renal biopsies, the CD24‐positive cells represent tubular cells with a deviant phenotype, characterized by a distinct morphology and marker expression. After acute tubular injury, these cells become more numerous. In healthy rat kidneys, these cells are not detectable, whereas after UUO, they appeared de novo – arguing against the notion that these cells represent a pre‐existing progenitor cell population. Our data indicate rather that these cells represent transiently dedifferentiated tubular cells involved in regeneration. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

AB - AbstractRegeneration of injured tubular cells occurs after acute tubular necrosis primarily from intrinsic renal cells. This may occur from a pre‐existing intratubular stem/progenitor cell population or from any surviving proximal tubular cell. In this study, we characterize a CD24‐, CD133‐, and vimentin‐positive subpopulation of cells scattered throughout the proximal tubule in normal human kidney. Compared to adjacent ‘normal’ proximal tubular cells, these CD24‐positive cells contained less cytoplasm, fewer mitochondria, and no brush border. In addition, 49 marker proteins are described that are expressed within the proximal tubules in a similar scattered pattern. For eight of these markers, we confirmed co‐localization with CD24. In human biopsies of patients with acute tubular necrosis (ATN), the number of CD24‐positive tubular cells was increased. In both normal human kidneys and the ATN biopsies, around 85% of proliferating cells were CD24‐positive – indicating that this cell population participates in tubular regeneration. In healthy rat kidneys, the novel cell subpopulation was absent. However, upon unilateral ureteral obstruction (UUO), the novel cell population was detected in significant amounts in the injured kidney. In summary, in human renal biopsies, the CD24‐positive cells represent tubular cells with a deviant phenotype, characterized by a distinct morphology and marker expression. After acute tubular injury, these cells become more numerous. In healthy rat kidneys, these cells are not detectable, whereas after UUO, they appeared de novo – arguing against the notion that these cells represent a pre‐existing progenitor cell population. Our data indicate rather that these cells represent transiently dedifferentiated tubular cells involved in regeneration. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

U2 - 10.1002/path.4125

DO - 10.1002/path.4125

M3 - Article

SN - 0022-3417

VL - 229

SP - 645

EP - 659

JO - The Journal of Pathology

JF - The Journal of Pathology

IS - 5

ER -

Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration

Abstract

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