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dc.contributor.authorScharf, Gesine M.
dc.contributor.authorKilian, Katja
dc.contributor.authorCordero, Julio
dc.contributor.authorWang, Yong
dc.contributor.authorGrund, Andrea
dc.contributor.authorHofmann, Melanie
dc.contributor.authorFroese, Natali
dc.contributor.authorWang, Xue
dc.contributor.authorKispert, Andreas
dc.contributor.authorKist, Ralf
dc.contributor.authorConway, Simon J.
dc.contributor.authorGeffers, Robert
dc.contributor.authorWollert, Kai C.
dc.contributor.authorDobreva, Gergana
dc.contributor.authorBauersachs, Johann
dc.contributor.authorHeineke, Joerg
dc.creatorScharf, G.
dc.date.accessioned2019-09-06T08:52:15Z
dc.date.available2019-09-06T08:52:15Z
dc.date.issued2019-08-08
dc.identifier.citationJCI Insight. 2019 Jul 16;5. pii: 126721. doi: 10.1172/jci.insight.126721.en_US
dc.identifier.pmid31310588
dc.identifier.doi10.1172/jci.insight.126721
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85070818930&origin=inward
dc.identifier.urihttp://hdl.handle.net/10033/621929
dc.description.abstractFibrotic scarring drives the progression of heart failure after myocardial infarction (MI). Therefore, the development of specific treatment regimens to counteract fibrosis is of high clinical relevance. The transcription factor SOX9 functions as an important regulator during embryogenesis, but recent data point towards an additional causal role in organ fibrosis. We show here that SOX9 is upregulated in the scar after MI in mice. Fibroblast specific deletion of Sox9 ameliorated MI-induced left ventricular dysfunction, dilatation and myocardial scarring in vivo. Unexpectedly, deletion of Sox9 also potently eliminated persisting leukocyte infiltration of the scar in the chronic phase after MI. RNA-sequencing from the infarct scar revealed that Sox9 deletion in fibroblasts resulted in strongly downregulated expression of genes related to extracellular matrix, proteolysis and inflammation. Importantly, Sox9 deletion in isolated cardiac fibroblasts in vitro similarly affected gene expression as in the cardiac scar and reduced fibroblast proliferation, migration and contraction capacity. Together, our data demonstrate that fibroblast SOX9 functions as a master regulator of cardiac fibrosis and inflammation and might constitute a novel therapeutic target during MI.en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.ispartofJCI Insight
dc.relation.ispartofseries15en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleInactivation of Sox9 in fibroblasts reduces cardiac fibrosis and inflammationen_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalJCI Insighten_US
dc.identifier.eid2-s2.0-85070818930
dc.identifier.scopusidSCOPUS_ID:85070818930
dc.relation.volume4
refterms.dateFOA2019-09-06T08:52:17Z


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