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REV-ERB is essential in cardiac fibroblasts homeostasis

REV-ERB agonists have shown antifibrotic effects in the heart and other organs. The function of REV-ERB in the cardiac fibroblasts remains unstudied. Here, we characterize the functional difference of REV-ERB in mouse embryonic fibroblasts and cardiac fibroblasts using genetic deletion of REV-ERBα a...

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Autores principales: Luo, Xiaokang, Song, Shiyang, Qi, Lei, Tien, Chih-Liang, Li, Hui, Xu, Weiyi, Mathuram, Theodore Lemuel, Burris, Thomas, Zhao, Yuanbiao, Sun, Zheng, Zhang, Lilei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662302/
https://www.ncbi.nlm.nih.gov/pubmed/36386186
http://dx.doi.org/10.3389/fphar.2022.899628
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author Luo, Xiaokang
Song, Shiyang
Qi, Lei
Tien, Chih-Liang
Li, Hui
Xu, Weiyi
Mathuram, Theodore Lemuel
Burris, Thomas
Zhao, Yuanbiao
Sun, Zheng
Zhang, Lilei
author_facet Luo, Xiaokang
Song, Shiyang
Qi, Lei
Tien, Chih-Liang
Li, Hui
Xu, Weiyi
Mathuram, Theodore Lemuel
Burris, Thomas
Zhao, Yuanbiao
Sun, Zheng
Zhang, Lilei
author_sort Luo, Xiaokang
collection PubMed
description REV-ERB agonists have shown antifibrotic effects in the heart and other organs. The function of REV-ERB in the cardiac fibroblasts remains unstudied. Here, we characterize the functional difference of REV-ERB in mouse embryonic fibroblasts and cardiac fibroblasts using genetic deletion of REV-ERBα and ß in vitro. We show that REV-ERB α/β double deleted cardiac fibroblasts have reduced viability and proliferation, but increased migration and myofibroblasts activation. Thus, REV-ERB α/β has essential cell-autonomous role in cardiac fibroblasts in maintaining them in a healthy, quiescent state. We also show that existing REV-ERB agonist SR9009 strongly suppresses cardiac fibroblasts activation but in a REV-ERB-independent manner highlighting the need to develop novel REV-ERB agonists for treating cardiac fibrosis.
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spelling pubmed-96623022022-11-15 REV-ERB is essential in cardiac fibroblasts homeostasis Luo, Xiaokang Song, Shiyang Qi, Lei Tien, Chih-Liang Li, Hui Xu, Weiyi Mathuram, Theodore Lemuel Burris, Thomas Zhao, Yuanbiao Sun, Zheng Zhang, Lilei Front Pharmacol Pharmacology REV-ERB agonists have shown antifibrotic effects in the heart and other organs. The function of REV-ERB in the cardiac fibroblasts remains unstudied. Here, we characterize the functional difference of REV-ERB in mouse embryonic fibroblasts and cardiac fibroblasts using genetic deletion of REV-ERBα and ß in vitro. We show that REV-ERB α/β double deleted cardiac fibroblasts have reduced viability and proliferation, but increased migration and myofibroblasts activation. Thus, REV-ERB α/β has essential cell-autonomous role in cardiac fibroblasts in maintaining them in a healthy, quiescent state. We also show that existing REV-ERB agonist SR9009 strongly suppresses cardiac fibroblasts activation but in a REV-ERB-independent manner highlighting the need to develop novel REV-ERB agonists for treating cardiac fibrosis. Frontiers Media S.A. 2022-10-31 /pmc/articles/PMC9662302/ /pubmed/36386186 http://dx.doi.org/10.3389/fphar.2022.899628 Text en Copyright © 2022 Luo, Song, Qi, Tien, Li, Xu, Mathuram, Burris, Zhao, Sun and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Luo, Xiaokang
Song, Shiyang
Qi, Lei
Tien, Chih-Liang
Li, Hui
Xu, Weiyi
Mathuram, Theodore Lemuel
Burris, Thomas
Zhao, Yuanbiao
Sun, Zheng
Zhang, Lilei
REV-ERB is essential in cardiac fibroblasts homeostasis
title REV-ERB is essential in cardiac fibroblasts homeostasis
title_full REV-ERB is essential in cardiac fibroblasts homeostasis
title_fullStr REV-ERB is essential in cardiac fibroblasts homeostasis
title_full_unstemmed REV-ERB is essential in cardiac fibroblasts homeostasis
title_short REV-ERB is essential in cardiac fibroblasts homeostasis
title_sort rev-erb is essential in cardiac fibroblasts homeostasis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662302/
https://www.ncbi.nlm.nih.gov/pubmed/36386186
http://dx.doi.org/10.3389/fphar.2022.899628
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