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Identification of Renal Progenitor-Like Tubular Cells that Participate in the Regeneration Processes of the Kidney

Third Department of Internal Medicine, Gunma University, School of Medicine, Maebashi, Japan

Correspondence to Dr. Akito Maeshima, Third Department of Internal Medicine, Gunma University School of Medicine, 3-39-15, Showa, Maebashi 371-8511, Japan. Phone: +81-27-220-8166; Fax: +81-27-220-8173; E-mail: amaeshima{at}ucsd.edu

ABSTRACT. The present study was conducted to explore renal progenitor-like cells that are actively engaged in tubular regeneration after injury. For addressing this issue, the existence of label-retaining cells (LRC; slow-cycling cells) in normal rat kidneys by in vivo bromodeoxyuridine (BrdU) labeling was examined. LRC were scattering among renal epithelial tubular cells of normal rat kidneys. During the recovery after renal ischemia, LRC underwent cell division and most of them became positive for proliferating cell nuclear antigen. In contrast, proliferating cell nuclear antigen–positive but BrdU-negative tubular cells were rarely observed, suggesting that cells proliferating during tubular regeneration are essentially derived from LRC. At an early phase of tubular regeneration, descendants of LRC expressed a mesenchymal marker, vimentin, and eventually became positive for an epithelial marker, E-cadherin, after multiple cell divisions. These findings suggested that LRC function as a source of regenerating cells to replace injured cells. Collectively, it was concluded that LRC are renal progenitor-like tubular cells that provide regenerating cells, which actively proliferate and eventually differentiate into epithelial cell, during tubular regeneration. It may be possible to regenerate renal tubules in vivo through the activation of LRC.

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