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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9662302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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