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Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway
Angiotensin II (Ang II) is a key contributor to glomerular disease by predominantly resulting in podocyte injury, whereas the underlying molecular mechanisms has not been fully understood. This study aimed to investigate if and how ADP-ribosylation factor 6 (Arf6), a small GTP-binding protein, invol...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051060/ https://www.ncbi.nlm.nih.gov/pubmed/32119711 http://dx.doi.org/10.1371/journal.pone.0229747 |
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author | Che, Guanghua Gao, Hang Hu, Qibo Xie, Hongchang Zhang, Yunfeng |
author_facet | Che, Guanghua Gao, Hang Hu, Qibo Xie, Hongchang Zhang, Yunfeng |
author_sort | Che, Guanghua |
collection | PubMed |
description | Angiotensin II (Ang II) is a key contributor to glomerular disease by predominantly resulting in podocyte injury, whereas the underlying molecular mechanisms has not been fully understood. This study aimed to investigate if and how ADP-ribosylation factor 6 (Arf6), a small GTP-binding protein, involves Ang II-induced cellular injury in cultured human podocytes. Cellular injury was evaluated with caspase 3 activity, reactive oxygen species (ROS) level and TUNEL assay. Arf6 activity was measured using an Arf6-GTP Pull-Down Assay. Ang II significantly enhanced Arf6 expressions accompanied by increase of Arf6-GTP. The TUNEL-positive cells as well as activated caspase 3, NADPH oxidase 4 protein (Nox4) and ROS levels were dramatically increased in Ang II-treated podocytes, which was prevented by secinH3, an Arf6 activity inhibitor. Induction of ROS by Ang II was inhibited in podocytes with Nox4 knockdown. Ang II-induced elevation of Nox4 and ROS was prevented by Arf6 knockdown. Phpspho-Erk1/2(Thr202/Tyr204) levels were upregulated remarkably following Ang II treatment, and Erk inhibitor LY3214996 significantly downregulated Nox4 expression. In addition, Ang II decreased CD2AP expression. Overexpression of CD2AP prevented Ang II-induced upregulation of Arf6-GTP. Our data demonstrated that Ang II promotes ROS production and podocytes injury through activation of Arf6-Erk1/2-Nox4 signaling. We also provided evidence that Ang II activates Arf6 by degradation of CD2AP. |
format | Online Article Text |
id | pubmed-7051060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70510602020-03-12 Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway Che, Guanghua Gao, Hang Hu, Qibo Xie, Hongchang Zhang, Yunfeng PLoS One Research Article Angiotensin II (Ang II) is a key contributor to glomerular disease by predominantly resulting in podocyte injury, whereas the underlying molecular mechanisms has not been fully understood. This study aimed to investigate if and how ADP-ribosylation factor 6 (Arf6), a small GTP-binding protein, involves Ang II-induced cellular injury in cultured human podocytes. Cellular injury was evaluated with caspase 3 activity, reactive oxygen species (ROS) level and TUNEL assay. Arf6 activity was measured using an Arf6-GTP Pull-Down Assay. Ang II significantly enhanced Arf6 expressions accompanied by increase of Arf6-GTP. The TUNEL-positive cells as well as activated caspase 3, NADPH oxidase 4 protein (Nox4) and ROS levels were dramatically increased in Ang II-treated podocytes, which was prevented by secinH3, an Arf6 activity inhibitor. Induction of ROS by Ang II was inhibited in podocytes with Nox4 knockdown. Ang II-induced elevation of Nox4 and ROS was prevented by Arf6 knockdown. Phpspho-Erk1/2(Thr202/Tyr204) levels were upregulated remarkably following Ang II treatment, and Erk inhibitor LY3214996 significantly downregulated Nox4 expression. In addition, Ang II decreased CD2AP expression. Overexpression of CD2AP prevented Ang II-induced upregulation of Arf6-GTP. Our data demonstrated that Ang II promotes ROS production and podocytes injury through activation of Arf6-Erk1/2-Nox4 signaling. We also provided evidence that Ang II activates Arf6 by degradation of CD2AP. Public Library of Science 2020-03-02 /pmc/articles/PMC7051060/ /pubmed/32119711 http://dx.doi.org/10.1371/journal.pone.0229747 Text en © 2020 Che et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Che, Guanghua Gao, Hang Hu, Qibo Xie, Hongchang Zhang, Yunfeng Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway |
title | Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway |
title_full | Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway |
title_fullStr | Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway |
title_full_unstemmed | Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway |
title_short | Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway |
title_sort | angiotensin ii promotes podocyte injury by activating arf6-erk1/2-nox4 signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051060/ https://www.ncbi.nlm.nih.gov/pubmed/32119711 http://dx.doi.org/10.1371/journal.pone.0229747 |
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