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| 001 | 136822 | ||
| 005 | 20240229111723.0 | ||
| 024 | 7 | _ | |a 10.15252/emmm.201708536 |2 doi |
| 024 | 7 | _ | |a pmid:29907596 |2 pmid |
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| 037 | _ | _ | |a DKFZ-2018-01260 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Tóth, András D |0 0000-0003-2746-9370 |b 0 |
| 245 | _ | _ | |a Inflammation leads through PGE/EP3 signaling to HDAC5/MEF2-dependent transcription in cardiac myocytes. |
| 260 | _ | _ | |a Weinheim |c 2018 |b Wiley-VCH |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1550485670_680 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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 second of protein kinase D. Both pathways converge on and inactivate histone deacetylase 5 (HDAC5) and thereby de-repress MEF2. In vivo, endotoxemia in MEF2-reporter mice induced upregulation of PGE2 and MEF2 activation. Our findings provide an unexpected new link between inflammation and cardiac remodeling by de-repression of MEF2 through HDAC5 inactivation, which has potential implications for new strategies to treat inflammatory cardiomyopathies. |
| 536 | _ | _ | |a 322 - Genetics and Pathophysiology (POF3-322) |0 G:(DE-HGF)POF3-322 |c POF3-322 |f POF III |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 700 | 1 | _ | |a Schell, Richard |b 1 |
| 700 | 1 | _ | |a Lévay, Magdolna |b 2 |
| 700 | 1 | _ | |a Vettel, Christiane |b 3 |
| 700 | 1 | _ | |a Theis, Philipp |b 4 |
| 700 | 1 | _ | |a Haslinger, Clemens |b 5 |
| 700 | 1 | _ | |a Alban, Felix |b 6 |
| 700 | 1 | _ | |a Werhahn, Stefanie |b 7 |
| 700 | 1 | _ | |a Frischbier, Lina |b 8 |
| 700 | 1 | _ | |a Krebs-Haupenthal, Jutta |b 9 |
| 700 | 1 | _ | |a Thomas, Dominique |b 10 |
| 700 | 1 | _ | |a Gröne, Hermann-Josef |0 P:(DE-He78)00a2ea610aee4a8fca32908fc3d02e91 |b 11 |u dkfz |
| 700 | 1 | _ | |a Avkiran, Metin |b 12 |
| 700 | 1 | _ | |a Katus, Hugo A |b 13 |
| 700 | 1 | _ | |a Wieland, Thomas |b 14 |
| 700 | 1 | _ | |a Backs, Johannes |0 0000-0002-2322-2699 |b 15 |
| 773 | _ | _ | |a 10.15252/emmm.201708536 |g Vol. 10, no. 7, p. e8536 - |0 PERI:(DE-600)2485479-7 |n 7 |p e8536 - |t EMBO molecular medicine |v 10 |y 2018 |x 1757-4684 |
| 909 | C | O | |p VDB |o oai:inrepo02.dkfz.de:136822 |
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