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Epidermal growth factor receptor activation is essential for kidney fibrosis development

Fibrosis is the progressive accumulation of excess extracellular matrix and can cause organ failure. Fibrosis can affect nearly every organ including kidney and there is no specific treatment currently. Although Epidermal Growth Factor Receptor (EGFR) signaling pathway has been implicated in develop...

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Autores principales: Cao, Shirong, Pan, Yu, Terker, Andrew S., Arroyo Ornelas, Juan Pablo, Wang, Yinqiu, Tang, Jiaqi, Niu, Aolei, Kar, Sarah Abu, Jiang, Mengdi, Luo, Wentian, Dong, Xinyu, Fan, Xiaofeng, Wang, Suwan, Wilson, Matthew H., Fogo, Agnes, Zhang, Ming-Zhi, Harris, Raymond C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645887/
https://www.ncbi.nlm.nih.gov/pubmed/37963889
http://dx.doi.org/10.1038/s41467-023-43226-x
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author Cao, Shirong
Pan, Yu
Terker, Andrew S.
Arroyo Ornelas, Juan Pablo
Wang, Yinqiu
Tang, Jiaqi
Niu, Aolei
Kar, Sarah Abu
Jiang, Mengdi
Luo, Wentian
Dong, Xinyu
Fan, Xiaofeng
Wang, Suwan
Wilson, Matthew H.
Fogo, Agnes
Zhang, Ming-Zhi
Harris, Raymond C.
author_facet Cao, Shirong
Pan, Yu
Terker, Andrew S.
Arroyo Ornelas, Juan Pablo
Wang, Yinqiu
Tang, Jiaqi
Niu, Aolei
Kar, Sarah Abu
Jiang, Mengdi
Luo, Wentian
Dong, Xinyu
Fan, Xiaofeng
Wang, Suwan
Wilson, Matthew H.
Fogo, Agnes
Zhang, Ming-Zhi
Harris, Raymond C.
author_sort Cao, Shirong
collection PubMed
description Fibrosis is the progressive accumulation of excess extracellular matrix and can cause organ failure. Fibrosis can affect nearly every organ including kidney and there is no specific treatment currently. Although Epidermal Growth Factor Receptor (EGFR) signaling pathway has been implicated in development of kidney fibrosis, underlying mechanisms by which EGFR itself mediates kidney fibrosis have not been elucidated. We find that EGFR expression increases in interstitial myofibroblasts in human and mouse fibrotic kidneys. Selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins. In vivo and in vitro studies and single-nucleus RNA sequencing analysis demonstrate that EGFR activation does not induce myofibroblast transformation but is necessary for the initial pericyte/fibroblast migration and proliferation prior to subsequent myofibroblast transformation by TGF-ß or other profibrotic factors. These findings may also provide insight into development of fibrosis in other organs and in other conditions.
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spelling pubmed-106458872023-11-14 Epidermal growth factor receptor activation is essential for kidney fibrosis development Cao, Shirong Pan, Yu Terker, Andrew S. Arroyo Ornelas, Juan Pablo Wang, Yinqiu Tang, Jiaqi Niu, Aolei Kar, Sarah Abu Jiang, Mengdi Luo, Wentian Dong, Xinyu Fan, Xiaofeng Wang, Suwan Wilson, Matthew H. Fogo, Agnes Zhang, Ming-Zhi Harris, Raymond C. Nat Commun Article Fibrosis is the progressive accumulation of excess extracellular matrix and can cause organ failure. Fibrosis can affect nearly every organ including kidney and there is no specific treatment currently. Although Epidermal Growth Factor Receptor (EGFR) signaling pathway has been implicated in development of kidney fibrosis, underlying mechanisms by which EGFR itself mediates kidney fibrosis have not been elucidated. We find that EGFR expression increases in interstitial myofibroblasts in human and mouse fibrotic kidneys. Selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins. In vivo and in vitro studies and single-nucleus RNA sequencing analysis demonstrate that EGFR activation does not induce myofibroblast transformation but is necessary for the initial pericyte/fibroblast migration and proliferation prior to subsequent myofibroblast transformation by TGF-ß or other profibrotic factors. These findings may also provide insight into development of fibrosis in other organs and in other conditions. Nature Publishing Group UK 2023-11-14 /pmc/articles/PMC10645887/ /pubmed/37963889 http://dx.doi.org/10.1038/s41467-023-43226-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Cao, Shirong
Pan, Yu
Terker, Andrew S.
Arroyo Ornelas, Juan Pablo
Wang, Yinqiu
Tang, Jiaqi
Niu, Aolei
Kar, Sarah Abu
Jiang, Mengdi
Luo, Wentian
Dong, Xinyu
Fan, Xiaofeng
Wang, Suwan
Wilson, Matthew H.
Fogo, Agnes
Zhang, Ming-Zhi
Harris, Raymond C.
Epidermal growth factor receptor activation is essential for kidney fibrosis development
title Epidermal growth factor receptor activation is essential for kidney fibrosis development
title_full Epidermal growth factor receptor activation is essential for kidney fibrosis development
title_fullStr Epidermal growth factor receptor activation is essential for kidney fibrosis development
title_full_unstemmed Epidermal growth factor receptor activation is essential for kidney fibrosis development
title_short Epidermal growth factor receptor activation is essential for kidney fibrosis development
title_sort epidermal growth factor receptor activation is essential for kidney fibrosis development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645887/
https://www.ncbi.nlm.nih.gov/pubmed/37963889
http://dx.doi.org/10.1038/s41467-023-43226-x
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