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C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice

Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated t...

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Autores principales: Zhang, Liwen, Zhou, Fangfang, Yu, Xialian, Zhu, Yufei, Zhou, Ying, Liu, Jian, Liu, Yunzi, Ma, Qingyang, Zhang, Yuchao, Wang, Weiming, Chen, Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746733/
https://www.ncbi.nlm.nih.gov/pubmed/31527620
http://dx.doi.org/10.1038/s41419-019-1933-2
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author Zhang, Liwen
Zhou, Fangfang
Yu, Xialian
Zhu, Yufei
Zhou, Ying
Liu, Jian
Liu, Yunzi
Ma, Qingyang
Zhang, Yuchao
Wang, Weiming
Chen, Nan
author_facet Zhang, Liwen
Zhou, Fangfang
Yu, Xialian
Zhu, Yufei
Zhou, Ying
Liu, Jian
Liu, Yunzi
Ma, Qingyang
Zhang, Yuchao
Wang, Weiming
Chen, Nan
author_sort Zhang, Liwen
collection PubMed
description Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of C/EBPα in podocyte senescence and kidney aging by generating a genetically modified mouse model of chronological aging in which C/EBPα was selectively deleted in podocytes and by overexpressing C/EBPα in cultured podocytes, in which premature senescence was induced by treatment with adriamycin. Moreover, we illuminated the mechanisms by which podocyte senescence causes tubular impairment by stimulating HK-2 cells with bovine serum albumin (BSA) and chloroquine. Our findings suggest that C/EBPα knockout in podocytes aggravates podocyte senescence through the AMPK/mTOR pathway, leading to glomerulosclerosis, and that subsequent albuminuria exacerbates the epithelial–mesenchymal transdifferentiation of senescent tubular cells by suppressing autophagy. These observations highlight the importance of C/EBPα as a new potential target in kidney aging.
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spelling pubmed-67467332019-09-17 C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice Zhang, Liwen Zhou, Fangfang Yu, Xialian Zhu, Yufei Zhou, Ying Liu, Jian Liu, Yunzi Ma, Qingyang Zhang, Yuchao Wang, Weiming Chen, Nan Cell Death Dis Article Kidney aging leads to an increased incidence of end-stage renal disease (ESRD) in the elderly, and aging is a complex biological process controlled by signaling pathways and transcription factors. Podocyte senescence plays a central role in injury resulting from kidney aging. Here, we demonstrated the critical role of C/EBPα in podocyte senescence and kidney aging by generating a genetically modified mouse model of chronological aging in which C/EBPα was selectively deleted in podocytes and by overexpressing C/EBPα in cultured podocytes, in which premature senescence was induced by treatment with adriamycin. Moreover, we illuminated the mechanisms by which podocyte senescence causes tubular impairment by stimulating HK-2 cells with bovine serum albumin (BSA) and chloroquine. Our findings suggest that C/EBPα knockout in podocytes aggravates podocyte senescence through the AMPK/mTOR pathway, leading to glomerulosclerosis, and that subsequent albuminuria exacerbates the epithelial–mesenchymal transdifferentiation of senescent tubular cells by suppressing autophagy. These observations highlight the importance of C/EBPα as a new potential target in kidney aging. Nature Publishing Group UK 2019-09-17 /pmc/articles/PMC6746733/ /pubmed/31527620 http://dx.doi.org/10.1038/s41419-019-1933-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Liwen
Zhou, Fangfang
Yu, Xialian
Zhu, Yufei
Zhou, Ying
Liu, Jian
Liu, Yunzi
Ma, Qingyang
Zhang, Yuchao
Wang, Weiming
Chen, Nan
C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice
title C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice
title_full C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice
title_fullStr C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice
title_full_unstemmed C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice
title_short C/EBPα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice
title_sort c/ebpα deficiency in podocytes aggravates podocyte senescence and kidney injury in aging mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746733/
https://www.ncbi.nlm.nih.gov/pubmed/31527620
http://dx.doi.org/10.1038/s41419-019-1933-2
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