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Cytoresistance after acute kidney injury is limited to the recovery period of proximal tubule integrity and possibly involves Hippo‐YAP signaling

Rat proximal tubule (PT) cells that have recovered from severe acute kidney injury induced by uranyl acetate (UA) develop cytoresistance to subsequent UA treatments. We reported that enhanced G1 arrest might contribute to cytoresistance. Herein, we examined these mechanisms by investigating Yes‐asso...

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Autores principales: Iwakura, Takamasa, Fujigaki, Yoshihide, Fujikura, Tomoyuki, Tsuji, Takayuki, Ohashi, Naro, Kato, Akihiko, Yasuda, Hideo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471447/
https://www.ncbi.nlm.nih.gov/pubmed/28611154
http://dx.doi.org/10.14814/phy2.13310
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author Iwakura, Takamasa
Fujigaki, Yoshihide
Fujikura, Tomoyuki
Tsuji, Takayuki
Ohashi, Naro
Kato, Akihiko
Yasuda, Hideo
author_facet Iwakura, Takamasa
Fujigaki, Yoshihide
Fujikura, Tomoyuki
Tsuji, Takayuki
Ohashi, Naro
Kato, Akihiko
Yasuda, Hideo
author_sort Iwakura, Takamasa
collection PubMed
description Rat proximal tubule (PT) cells that have recovered from severe acute kidney injury induced by uranyl acetate (UA) develop cytoresistance to subsequent UA treatments. We reported that enhanced G1 arrest might contribute to cytoresistance. Herein, we examined these mechanisms by investigating Yes‐associated protein (YAP), a regulator of cell number, and survivin, a downstream mediator of YAP that inhibits apoptosis. Rats pretreated with saline (vehicle group) or UA (AKI group) were injected with UA 2 weeks, 2 months, or 6 months after treatment. Cytoresistance, evaluated by serum creatinine, was observed at 2 weeks, was attenuated at 2 months, and was lost at 6 months in the AKI group. Based on immunohistochemistry, overexpressed YAP/survivin in PT cells and an increased number of PT cells was found before the second insult at 2 weeks, regressed gradually, and returned to a normal value by 6 months in the AKI group. Cell cycle status, assessed by flow cytometry, was equivalent in all groups before the second insult. However, early G1 phase (cyclin D1−) and p27+ PT cells increased in the AKI group compared to those in the vehicle group until 2 months, but were comparable to those in the vehicle group at 6 months. p21+ PT cells increased at 2 weeks, but normalized by 2 months. Thus, PT cells that have recovered from AKI transiently overexpress YAP/survivin, probably inhibiting apoptosis and resulting in acquired cytoresistance. This effect occurs until PT remodeling is complete, subceullular PT integrity is restored, and cell numbers are normalized.
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spelling pubmed-54714472017-06-21 Cytoresistance after acute kidney injury is limited to the recovery period of proximal tubule integrity and possibly involves Hippo‐YAP signaling Iwakura, Takamasa Fujigaki, Yoshihide Fujikura, Tomoyuki Tsuji, Takayuki Ohashi, Naro Kato, Akihiko Yasuda, Hideo Physiol Rep Original Research Rat proximal tubule (PT) cells that have recovered from severe acute kidney injury induced by uranyl acetate (UA) develop cytoresistance to subsequent UA treatments. We reported that enhanced G1 arrest might contribute to cytoresistance. Herein, we examined these mechanisms by investigating Yes‐associated protein (YAP), a regulator of cell number, and survivin, a downstream mediator of YAP that inhibits apoptosis. Rats pretreated with saline (vehicle group) or UA (AKI group) were injected with UA 2 weeks, 2 months, or 6 months after treatment. Cytoresistance, evaluated by serum creatinine, was observed at 2 weeks, was attenuated at 2 months, and was lost at 6 months in the AKI group. Based on immunohistochemistry, overexpressed YAP/survivin in PT cells and an increased number of PT cells was found before the second insult at 2 weeks, regressed gradually, and returned to a normal value by 6 months in the AKI group. Cell cycle status, assessed by flow cytometry, was equivalent in all groups before the second insult. However, early G1 phase (cyclin D1−) and p27+ PT cells increased in the AKI group compared to those in the vehicle group until 2 months, but were comparable to those in the vehicle group at 6 months. p21+ PT cells increased at 2 weeks, but normalized by 2 months. Thus, PT cells that have recovered from AKI transiently overexpress YAP/survivin, probably inhibiting apoptosis and resulting in acquired cytoresistance. This effect occurs until PT remodeling is complete, subceullular PT integrity is restored, and cell numbers are normalized. John Wiley and Sons Inc. 2017-06-14 /pmc/articles/PMC5471447/ /pubmed/28611154 http://dx.doi.org/10.14814/phy2.13310 Text en © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Iwakura, Takamasa
Fujigaki, Yoshihide
Fujikura, Tomoyuki
Tsuji, Takayuki
Ohashi, Naro
Kato, Akihiko
Yasuda, Hideo
Cytoresistance after acute kidney injury is limited to the recovery period of proximal tubule integrity and possibly involves Hippo‐YAP signaling
title Cytoresistance after acute kidney injury is limited to the recovery period of proximal tubule integrity and possibly involves Hippo‐YAP signaling
title_full Cytoresistance after acute kidney injury is limited to the recovery period of proximal tubule integrity and possibly involves Hippo‐YAP signaling
title_fullStr Cytoresistance after acute kidney injury is limited to the recovery period of proximal tubule integrity and possibly involves Hippo‐YAP signaling
title_full_unstemmed Cytoresistance after acute kidney injury is limited to the recovery period of proximal tubule integrity and possibly involves Hippo‐YAP signaling
title_short Cytoresistance after acute kidney injury is limited to the recovery period of proximal tubule integrity and possibly involves Hippo‐YAP signaling
title_sort cytoresistance after acute kidney injury is limited to the recovery period of proximal tubule integrity and possibly involves hippo‐yap signaling
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471447/
https://www.ncbi.nlm.nih.gov/pubmed/28611154
http://dx.doi.org/10.14814/phy2.13310
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