Publication Date
1-1-2022
Journal
Frontiers in Pharmacology
DOI
10.3389/fphar.2022.899628
PMID
36386186
PMCID
PMC9662302
Published Open-Access
no
Keywords
REV-ERB, fibroblast activation, SR9009, cardiac fibroblasts, TGFβ
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.
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Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Medical Sciences Commons
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