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http://purl.uniprot.org/citations/28809397http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28809397http://www.w3.org/2000/01/rdf-schema#comment"Endocardial fibroelastosis (EFE) refers to the thickening of the ventricular endocardium as a result of de novo deposition of subendocardial fibrous tissue layers during neonatal heart development. The origin of EFE fibroblasts is proposed to be postnatal endocardial cells that undergo an aberrant endothelial-to-mesenchymal transition (EndMT). Genetic lineage tracing of endocardial cells with the inducible endocardial Cre line Npr3-CreER and the endothelial cell tracing line Cdh5-CreER on an EFE-like model did not reveal any contribution of neonatal endocardial cells to fibroblasts in the EFE-like tissues. Instead, lineage tracing of embryonic epicardium by Wt1-CreER suggested that epicardium-derived mesenchymal cells (MCs) served as the major source of EFE fibroblasts. By labeling MCs using Sox9-CreER, we confirmed that MCs of the embryonic heart expand and contribute to the majority of neonatal EFE fibroblasts. During this pathological process, TGFβ signaling, the key mediator of fibroblasts activation, was highly upregulated in the EFE-like tissues. Targeting TGFβ signaling by administration of its antagonist bone morphogenetic protein 7 effectively reduced fibroblast accumulation and tissue fibrosis in the EFE-like model. Our study provides genetic evidence that excessive fibroblasts in the EFE-like tissues mainly originate from the epicardium-derived MCs through epicardial to mesenchymal transition (EpiMT). These EpiMT-derived fibroblasts within the EFE-like tissues could serve as a potential therapeutic target."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.org/dc/terms/identifier"doi:10.1038/cr.2017.103"xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Chen T."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Huang X."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Liu Q."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Li Y."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Qiao Z."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Tian X."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Wang Y."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Zhang H."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Wang F."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Zhang L."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Yu Y."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Wang H."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Zhou B."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Zhang L.'"xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Tang J."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"He L."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Liu K."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Hu R."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Pu W."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Wang Q.D."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/author"Lui K.O."xsd:string
http://purl.uniprot.org/citations/28809397http://purl.uniprot.org/core/date"2017"xsd:gYear