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NDT Advance Access published online on April 25, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp199
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Cell division and phenotypic regression of proximal tubular cells in response to uranyl acetate insult in rats

Yoshihide Fujigaki, Masanori Sakakima, Yuan Sun, Tomoyuki Fujikura, Takayuki Tsuji, Hideo Yasuda and Akira Hishida

First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan

Correspondence and offprint requests to: Yoshihide Fujigaki; E-mail: yf0516{at}hama-med.ac.jp



  Abstract

Background. We examined whether dedifferentiation is necessary for cell division of proximal tubule (PT) cells after acute PT injury.

Methods. Rats were injected with a low (0.2 mg/kg) or high (4 mg/kg) dose of uranyl acetate (UA) to induce acute PT injury. Proliferating PT cells were labelled with bromodeoxyuridine (BrdU) before sacrifice. Renal tissues were examined by double labelling of BrdU and megalin, aquaporin 1 (AQP1), Na+–K+ATPase or vimentin, and by immunoelectron microscopy for BrdU+ cells.

Results. Under normal conditions, BrdU+ PT cells were positive for the PT phenotype (megalin-, AQP1- and Na+–K+ATPase positive and vimentine negative, a mesenchymal marker). Low-dose UA induced focal PT injury, and BrdU+ initially proliferating PT cells were found in the proximal three quarters of the S3 segment of nephron as early as 12 h, which maintained the PT phenotype and were vimentin negative. Proliferating PT cells showed low expression of the PT cell protein phenotype from Day 2 to Day 5 with vimentin expression from Day 2. High-dose UA induced severe PT injury in the proximal three quarters of the S3 segment by Day 5. BrdU+ initially proliferating PT cells, which were found in distal areas of the S3 segment as early as Day 2, showed low expression of the PT protein phenotype but were vimentin positive. Immunoelectron microscopy showed mature PT morphology for BrdU+ PT cells in control rats. BrdU+ initially proliferating PT cells showed a relatively mature phenotype after low-dose UA in- sult but an immature phenotype after high-dose UA insult.

Conclusions. PT cells can initiate cell division without de- differentiation after mild PT injury by low-dose UA insult.

Keywords: acute renal failure; cell division; phenotype; proliferation; proximal tubule

Received for publication: 4. 1.09
Accepted in revised form: 7. 4.09


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