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Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4

Myocardial fibrosis can lead to ischemic damage of the myocardium, which can be life-threatening in severe cases. Cardiac fibroblast (CF) transdifferentiation is an important process in myocardial fibrosis. Fucoxanthin (FX) plays a key role in ameliorating myocardial fibrosis; however, its mechanism...

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Detalles Bibliográficos
Autores principales: Han, Jinxia, Zhang, Yanfang, Peng, Haisheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497131/
https://www.ncbi.nlm.nih.gov/pubmed/37699016
http://dx.doi.org/10.1371/journal.pone.0291469
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author Han, Jinxia
Zhang, Yanfang
Peng, Haisheng
author_facet Han, Jinxia
Zhang, Yanfang
Peng, Haisheng
author_sort Han, Jinxia
collection PubMed
description Myocardial fibrosis can lead to ischemic damage of the myocardium, which can be life-threatening in severe cases. Cardiac fibroblast (CF) transdifferentiation is an important process in myocardial fibrosis. Fucoxanthin (FX) plays a key role in ameliorating myocardial fibrosis; however, its mechanism of action is not fully understood. This study investigated the role of FX in the angiotensin II (Ang II)-induced transdifferentiation of CFs and its potential mechanisms of action. We found that FX inhibited Ang II-induced transdifferentiation of CFs. Simultaneously, FX downregulated bromodomain-containing protein 4 (BRD4) expression in CFs and increased nuclear expression of nuclear factorerythroid 2-related factor 2 (Nrf2). FX reverses AngII-induced inhibition of the Keap1/Nrf2/HO-1 pathway and elevates the level of reactive oxygen species (ROS). FX failed to reverse Ang II-induced changes in fibrosis-associated proteins and ROS levels after Nrf2 silencing. BRD4 silencing reversed the inhibitory effect of Ang II on the Keap1/Nrf2/HO-1 antioxidant signalling pathway. In conclusion, we demonstrated that FX inhibited Ang II-induced transdifferentiation of CFs and that this effect may be related to the activation of the Keap1/Nrf2/HO-1 pathway by reducing BRD4 expression and, ultimately, oxidative stress.
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spelling pubmed-104971312023-09-13 Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4 Han, Jinxia Zhang, Yanfang Peng, Haisheng PLoS One Research Article Myocardial fibrosis can lead to ischemic damage of the myocardium, which can be life-threatening in severe cases. Cardiac fibroblast (CF) transdifferentiation is an important process in myocardial fibrosis. Fucoxanthin (FX) plays a key role in ameliorating myocardial fibrosis; however, its mechanism of action is not fully understood. This study investigated the role of FX in the angiotensin II (Ang II)-induced transdifferentiation of CFs and its potential mechanisms of action. We found that FX inhibited Ang II-induced transdifferentiation of CFs. Simultaneously, FX downregulated bromodomain-containing protein 4 (BRD4) expression in CFs and increased nuclear expression of nuclear factorerythroid 2-related factor 2 (Nrf2). FX reverses AngII-induced inhibition of the Keap1/Nrf2/HO-1 pathway and elevates the level of reactive oxygen species (ROS). FX failed to reverse Ang II-induced changes in fibrosis-associated proteins and ROS levels after Nrf2 silencing. BRD4 silencing reversed the inhibitory effect of Ang II on the Keap1/Nrf2/HO-1 antioxidant signalling pathway. In conclusion, we demonstrated that FX inhibited Ang II-induced transdifferentiation of CFs and that this effect may be related to the activation of the Keap1/Nrf2/HO-1 pathway by reducing BRD4 expression and, ultimately, oxidative stress. Public Library of Science 2023-09-12 /pmc/articles/PMC10497131/ /pubmed/37699016 http://dx.doi.org/10.1371/journal.pone.0291469 Text en © 2023 Han et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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
Han, Jinxia
Zhang, Yanfang
Peng, Haisheng
Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4
title Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4
title_full Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4
title_fullStr Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4
title_full_unstemmed Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4
title_short Fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of BRD4
title_sort fucoxanthin inhibits cardiac fibroblast transdifferentiation by alleviating oxidative stress through downregulation of brd4
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497131/
https://www.ncbi.nlm.nih.gov/pubmed/37699016
http://dx.doi.org/10.1371/journal.pone.0291469
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