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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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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. |
format | Online Article Text |
id | pubmed-4865316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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