| http://purl.uniprot.org/citations/28891814 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28891814 | http://www.w3.org/2000/01/rdf-schema#comment | "The master cytokine TGF-β mediates tissue fibrosis associated with inflammation and tissue injury. TGF-β induces fibroblast activation and differentiation into myofibroblasts that secrete extracellular matrix proteins. Canonical TGF-β signaling mobilizes Smad2 and Smad3 transcription factors that control fibrosis by promoting gene expression. However, the importance of TGF-β-Smad2/3 signaling in fibroblast-mediated cardiac fibrosis has not been directly evaluated in vivo. Here, we examined pressure overload-induced cardiac fibrosis in fibroblast- and myofibroblast-specific inducible Cre-expressing mouse lines with selective deletion of the TGF-β receptors Tgfbr1/2, Smad2, or Smad3. Fibroblast-specific deletion of Tgfbr1/2 or Smad3, but not Smad2, markedly reduced the pressure overload-induced fibrotic response as well as fibrosis mediated by a heart-specific, latency-resistant TGF-β mutant transgene. Interestingly, cardiac fibroblast-specific deletion of Tgfbr1/2, but not Smad2/3, attenuated the cardiac hypertrophic response to pressure overload stimulation. Mechanistically, loss of Smad2/3 from tissue-resident fibroblasts attenuated injury-induced cellular expansion within the heart and the expression of fibrosis-mediating genes. Deletion of Smad2/3 or Tgfbr1/2 from cardiac fibroblasts similarly inhibited the gene program for fibrosis and extracellular matrix remodeling, although deletion of Tgfbr1/2 uniquely altered expression of an array of regulatory genes involved in cardiomyocyte homeostasis and disease compensation. These findings implicate TGF-β-Smad2/3 signaling in activated tissue-resident cardiac fibroblasts as principal mediators of the fibrotic response."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci94753"xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Lee S.J."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Liu R."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Fu X."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Karch J."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Khalil H."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Molkentin J.D."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Prasad V."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Correll R.N."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Huynh T."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Vagnozzi R.J."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Kanisicak O."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/author | "Schips T."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/pages | "3770-3783"xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/title | "Fibroblast-specific TGF-beta-Smad2/3 signaling underlies cardiac fibrosis."xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://purl.uniprot.org/core/volume | "127"xsd:string |
| http://purl.uniprot.org/citations/28891814 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28891814 |
| http://purl.uniprot.org/citations/28891814 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28891814 |
| http://purl.uniprot.org/uniprot/#_A0A097BW18-mappedCitation-28891814 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28891814 |
| http://purl.uniprot.org/uniprot/#_A0A097BW21-mappedCitation-28891814 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28891814 |
| http://purl.uniprot.org/uniprot/#_E9PZV6-mappedCitation-28891814 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28891814 |