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 

TITLE=REV-ERB is essential in cardiac fibroblasts homeostasis

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.899628

DOI=10.3389/fphar.2022.899628

ISSN=1663-9812

ABSTRACT=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 β. We show that REV-ERB is critical in maintaining cardiac fibroblasts in a healthy, quiescent state. REV-ERB agonist SR9009 strongly suppresses cardiac fibroblasts activation but in a REV-ERB-independent manner. These findings establish REV-ERB as a critical regulator of cardiac fibrosis and highlight the need to develop novel REV-ERB agonists for treating cardiac fibrosis.