title: A 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.
abstract: 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.
authors.affiliation: Internal Medicine I, Division of Nephrology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Iwakura
authors.affiliation: Internal Medicine I, Division of Nephrology, Hamamatsu University School of Medicine, Hamamatsu, Japan Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujigaki
authors.affiliation: Internal Medicine I, Division of Nephrology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujikura
authors.affiliation: Internal Medicine I, Division of Nephrology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Naro
authors.initials: N
authors.lastname: Ohashi
authors.affiliation: Blood Purification Unit, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kato
authors.affiliation: Internal Medicine I, Division of Nephrology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasuda
keywords: Cell cycle; G0‐G1 transition; G1 arrest; proximal tubule