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REV-ERB is essential in cardiac fibroblasts homeostasis

Authors :
Xiaokang Luo
Shiyang Song
Lei Qi
Chih-Liang Tien
Hui Li
Weiyi Xu
Theodore Lemuel Mathuram
Thomas Burris
Yuanbiao Zhao
Zheng Sun
Lilei Zhang
Source :
Frontiers in Pharmacology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

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 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.

Details

Language :
English
ISSN :
16639812
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Pharmacology
Publication Type :
Academic Journal
Accession number :
edsdoj.f968753e53384be3aaed3518750afe84
Document Type :
article
Full Text :
https://doi.org/10.3389/fphar.2022.899628