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=13

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=<p>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 <italic>ß in vitro</italic>. 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.</p>