Repair of injured proximal tubule does not involve specialized progenitors

Recently we have established that the kidney tubular epithelium is repaired by surviving epithelial cells. It is not known, however, whether a population of intratubular adult progenitor cells are responsible for this epithelial repair after acute kidney injury. In this study, we used an unbiased DN...

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Published in:	Proceedings of the National Academy of Sciences - PNAS 2011-05, Vol.108 (22), p.9226-9231
Main Authors:	Humphreys, Benjamin D, Czerniak, Suzanne, DiRocco, Derek P, Hasnain, Wirasat, Cheema, Rabia, Bonventre, Joseph V
Format:	Article
Language:	eng
Subjects:	adults Animals Biological Sciences Cell cycle Cell Differentiation Cell Division Cell growth Cell Movement Cell Proliferation Cell Survival Cellular biology cortex DNA DNA - metabolism DNA repair Epithelial cells epithelium Ischemia Ki-67 Antigen - biosynthesis Kidney cells Kidney diseases Kidney medulla Kidney Tubules, Proximal - metabolism Kidneys Male Mice Mice, Inbred C57BL Papillae Progenitor cells Proximal tubules Reperfusion Injury Stem cells Stem Cells - cytology Stochastic Processes Studies thymidine Thymidine - chemistry Time Factors
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Summary:	Recently we have established that the kidney tubular epithelium is repaired by surviving epithelial cells. It is not known, however, whether a population of intratubular adult progenitor cells are responsible for this epithelial repair after acute kidney injury. In this study, we used an unbiased DNA analog-based approach that does not rely on candidate markers to track multiple rounds of cell division in vivo. In the proximal tubule, robust thymidine analog incorporation was observed postinjury. Cell division was stochastic and enriched among cells that were injured and dedifferentiated. There was no evidence for the presence of a population of specialized progenitors that repeatedly divide in response to injury. Instead, these results indicate that after injury, new epithelial cells arise from self-duplication of surviving cells, most of which are injured. Because the renal papilla contains DNA label-retaining cells and has been proposed as a stem cell niche, we examined the proliferative behavior of these putative progenitors after ischemia-reperfusion injury. Although label-retaining cells in the renal papilla diminished with time after ischemia-reperfusion injury, they neither proliferated nor migrated to the outer medulla or cortex. Thus, nonlethally injured cells repopulate the kidney epithelium after injury in the absence of any specialized progenitor cell population.
ISSN:	0027-8424 1091-6490