Inflammation leads through PGE/EP₃ signaling to HDAC5/MEF2-dependent transcription in cardiac myocytes.

ABSTRACT: The myocyte enhancer factor 2 (MEF2) regulates transcription in cardiac myocytes and adverse remodeling of adult hearts. Activators of G protein-coupled receptors (GPCRs) have been reported to activate MEF2, but a comprehensive analysis of GPCR activators that regulate MEF2 has to our knowledge not been performed. Here, we tested several GPCR agonists regarding their ability to activate a MEF2 reporter in neonatal rat ventricular myocytes. The inflammatory mediator prostaglandin E₂ (PGE₂) strongly activated MEF2. Using pharmacological and protein-based inhibitors, we demonstrated that PGE₂ regulates MEF2 via the EP₃ receptor, the βγ subunit of G_i/o protein and two concomitantly activated downstream pathways. The first consists of Tiam1

SUBMITTER: Toth AD 

PROVIDER: S-EPMC6034133 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature