Open AccessA high ratio of G1 to G0 phase cells and an accumulation of G1 phase cells before S phase progression after injurious stimuli in the proximal tubule
Author(s) -
Iwakura Takamasa,
Fujigaki Yoshihide,
Fujikura Tomoyuki,
Ohashi Naro,
Kato Akihiko,
Yasuda Hideo
Publication year - 2014
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12173
Subject(s) - cell cycle , cell cycle progression , cell growth , apoptosis , flow cytometry , chemistry , microbiology and biotechnology , cell culture , cell , medicine , endocrinology , biology , biochemistry , genetics
Proximal tubule ( PT ) cells can proliferate explosively after injurious stimuli. To investigate this proliferative capacity, we examined cell cycle status and the expression of cyclin‐dependent kinase inhibitor p27, a G1 phase mediator, in PT cells after a proliferative or injurious stimulus. Rats were treated with lead acetate (proliferative stimulus) or uranyl acetate ( UA ; injurious stimulus). Isolated tubular cells were separated into PT and distal tubule ( DT ) cells by density‐gradient centrifugation. Cell cycle status was analyzed with flow cytometry by using the Hoechst 33342/pyronin Y method. Most PT and DT cells from control rats were in G0/G1 phase, with a higher percentage of PT cells than DT cells in G1 phase. Lead acetate and UA administration promoted the G0‐G1 transition and the accumulation of G1 phase cells before S phase progression. In PT cells from rats treated with lead acetate or a subnephrotoxic dose of UA , p27 levels increased or did not change, possibly reflecting G1 arrest. In contrast, p27 became undetectable before the appearance of apoptotic cells in rats treated with a nephrotoxic dose of UA . The decrease in p27 might facilitate rapid cell cycling. The decreased number of p27‐positive cells was associated with PT cell proliferation in renal tissues after a proliferative or injurious stimulus. The findings suggest that a high ratio of G1 to G0 phase cells and a rapid accumulation of G1 phase cells before S phase progression in the PT is a biological strategy for safe, timely, and explosive cell proliferation in response to injurious stimuli.