REV-ERB is essential in cardiac fibroblasts homeostasis

• Main Authors: Xiaokang Luo (Author), Shiyang Song (Author), Lei Qi (Author), Chih-Liang Tien (Author), Hui Li (Author), Weiyi Xu (Author), Theodore Lemuel Mathuram (Author), Thomas Burris (Author), Yuanbiao Zhao (Author), Zheng Sun (Author), Lilei Zhang (Author)
• Format: Book
• Published: Frontiers Media S.A., 2022-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1663-9812
10.3389/fphar.2022.899628