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ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway

Renal compensatory hypertrophy (RCH) restores normal kidney function after disease or loss of kidney tissue and is characterized by an increase in organ size due to cell enlargement and not to cell proliferation. In MDCK renal epithelial cells, silencing of the tight junction protein zona occludens...

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Autores principales: Domínguez-Calderón, Alaide, Ávila-Flores, Antonia, Ponce, Arturo, López-Bayghen, Esther, Calderón-Salinas, José-Víctor, Luis Reyes, José, Chávez-Munguía, Bibiana, Segovia, José, Angulo, Carla, Ramírez, Leticia, Gallego-Gutiérrez, Helios, Alarcón, Lourdes, Martín-Tapia, Dolores, Bautista-García, Pablo, González-Mariscal, Lorenza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865316/
https://www.ncbi.nlm.nih.gov/pubmed/27009203
http://dx.doi.org/10.1091/mbc.E15-08-0598
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author Domínguez-Calderón, Alaide
Ávila-Flores, Antonia
Ponce, Arturo
López-Bayghen, Esther
Calderón-Salinas, José-Víctor
Luis Reyes, José
Chávez-Munguía, Bibiana
Segovia, José
Angulo, Carla
Ramírez, Leticia
Gallego-Gutiérrez, Helios
Alarcón, Lourdes
Martín-Tapia, Dolores
Bautista-García, Pablo
González-Mariscal, Lorenza
author_facet Domínguez-Calderón, Alaide
Ávila-Flores, Antonia
Ponce, Arturo
López-Bayghen, Esther
Calderón-Salinas, José-Víctor
Luis Reyes, José
Chávez-Munguía, Bibiana
Segovia, José
Angulo, Carla
Ramírez, Leticia
Gallego-Gutiérrez, Helios
Alarcón, Lourdes
Martín-Tapia, Dolores
Bautista-García, Pablo
González-Mariscal, Lorenza
author_sort Domínguez-Calderón, Alaide
collection PubMed
description Renal compensatory hypertrophy (RCH) restores normal kidney function after disease or loss of kidney tissue and is characterized by an increase in organ size due to cell enlargement and not to cell proliferation. In MDCK renal epithelial cells, silencing of the tight junction protein zona occludens 2 (ZO-2 KD) induces cell hypertrophy by two mechanisms: prolonging the time that cells spend at the G1 phase of the cell cycle due to an increase in cyclin D1 level, and augmenting the rate of protein synthesis. The latter is triggered by the nuclear accumulation and increased transcriptional activity of Yes-associated protein (YAP), the main target of the Hippo pathway, which results in decreased expression of phosphatase and tensin homologue. This in turn increased the level of phosphatidylinositol (3,4,5)-triphosphate, which transactivates the Akt/mammalian target of rapamycin pathway, leading to activation of the kinase S6K1 and increased synthesis of proteins and cell size. In agreement, in a rat model of uninephrectomy, RCH is accompanied by decreased expression of ZO-2 and nuclear expression of YAP. Our results reveal a novel role of ZO-2 as a modulator of cell size.
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spelling pubmed-48653162016-07-30 ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway Domínguez-Calderón, Alaide Ávila-Flores, Antonia Ponce, Arturo López-Bayghen, Esther Calderón-Salinas, José-Víctor Luis Reyes, José Chávez-Munguía, Bibiana Segovia, José Angulo, Carla Ramírez, Leticia Gallego-Gutiérrez, Helios Alarcón, Lourdes Martín-Tapia, Dolores Bautista-García, Pablo González-Mariscal, Lorenza Mol Biol Cell Articles Renal compensatory hypertrophy (RCH) restores normal kidney function after disease or loss of kidney tissue and is characterized by an increase in organ size due to cell enlargement and not to cell proliferation. In MDCK renal epithelial cells, silencing of the tight junction protein zona occludens 2 (ZO-2 KD) induces cell hypertrophy by two mechanisms: prolonging the time that cells spend at the G1 phase of the cell cycle due to an increase in cyclin D1 level, and augmenting the rate of protein synthesis. The latter is triggered by the nuclear accumulation and increased transcriptional activity of Yes-associated protein (YAP), the main target of the Hippo pathway, which results in decreased expression of phosphatase and tensin homologue. This in turn increased the level of phosphatidylinositol (3,4,5)-triphosphate, which transactivates the Akt/mammalian target of rapamycin pathway, leading to activation of the kinase S6K1 and increased synthesis of proteins and cell size. In agreement, in a rat model of uninephrectomy, RCH is accompanied by decreased expression of ZO-2 and nuclear expression of YAP. Our results reveal a novel role of ZO-2 as a modulator of cell size. The American Society for Cell Biology 2016-05-15 /pmc/articles/PMC4865316/ /pubmed/27009203 http://dx.doi.org/10.1091/mbc.E15-08-0598 Text en © 2016 Domínguez-Calderón et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Domínguez-Calderón, Alaide
Ávila-Flores, Antonia
Ponce, Arturo
López-Bayghen, Esther
Calderón-Salinas, José-Víctor
Luis Reyes, José
Chávez-Munguía, Bibiana
Segovia, José
Angulo, Carla
Ramírez, Leticia
Gallego-Gutiérrez, Helios
Alarcón, Lourdes
Martín-Tapia, Dolores
Bautista-García, Pablo
González-Mariscal, Lorenza
ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway
title ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway
title_full ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway
title_fullStr ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway
title_full_unstemmed ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway
title_short ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway
title_sort zo-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of yap and the mtor pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865316/
https://www.ncbi.nlm.nih.gov/pubmed/27009203
http://dx.doi.org/10.1091/mbc.E15-08-0598
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