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 Gi/o protein and two concomitantly activated downstream pathways. The first consists of Tiam1, Rac1 and its effector p21-activated kinase 2, the seco

SUBMITTER: Dr. András, Dávid Tóth 

PROVIDER: S-SCDT-EMM-2017-08536 | biostudies-other |

REPOSITORIES: biostudies-other