| http://purl.uniprot.org/citations/27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27111286 | http://www.w3.org/2000/01/rdf-schema#comment | "Fibrosis is an ominous pathological process in failing myocardium, but its pathogenesis is poorly understood. We recently reported that loss of an extracellular matrix (ECM) protein, fibulin-2, protected against ventricular dysfunction after myocardial infarction (MI) in association with absence of activation of transforming growth factor (TGF)-β signaling and suppressed upregulation of ECM protein expression during myocardial remodeling. Here we investigated the role of fibulin-2 in the development of myocardial hypertrophy and fibrosis induced by continuous pressor-dosage of angiotensin II (Ang II) infusion. Both wild type (WT) and fibulin-2 null (Fbln2KO) mice developed comparable hypertension and myocardial hypertrophy by Ang II infusion. However, myocardial fibrosis with significant upregulation of collagen type I and III mRNA was only seen in WT but not in Fbln2KO mice.Transforming growth factor (TGF)-β1 mRNA and its downstream signal, Smad2, were significantly upregulated in WT by Ang II, whereas there were no Ang II-induced changes in Flbn2KO, suggesting fibulin-2 is necessary for Ang II-induced TGF-β signaling that induces myocardial fibrosis. To test whether fibulin-2 is sufficient for Ang II-induced TGF-β upregulation, isolated Flbn2KO cardiac fibroblasts were treated with Ang II after transfecting with fibulin-2 expression vector or pretreating with recombinant fibulin-2 protein. Ang II-induced TGF-β signaling in Fbln2KO cells was partially rescued by exogenous fibulin-2, suggesting that fibulin-2 is required and probably sufficient for Ang II-induced TGF-β activation. Smad2 phosphorylation was induced just by adding recombinant fibulin-2 to KO cells, suggesting that extracellular interaction between fibulin-2 and latent TGF-β triggered initial TGF-β activation. Our study indicates that Ang II cannot induce TGF-β activation without fibulin-2 and that fibulin-2 has an essential role in Ang II-induced TGF-β signaling and subsequent myocardial fibrosis. Fibulin-2 can be considered as a critical regulator of TGF-β that induces myocardial fibrosis."xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.org/dc/terms/identifier | "doi:10.1038/labinvest.2016.52"xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/author | "Dong H."xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/author | "Sasaki T."xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/author | "Khan S.A."xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/author | "Tsuda T."xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/author | "Chu M.L."xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/author | "Joyce J."xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/name | "Lab Invest"xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/pages | "773-783"xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/title | "Fibulin-2 is essential for angiotensin II-induced myocardial fibrosis mediated by transforming growth factor (TGF)-beta."xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://purl.uniprot.org/core/volume | "96"xsd:string |
| http://purl.uniprot.org/citations/27111286 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27111286 |
| http://purl.uniprot.org/citations/27111286 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27111286 |
| http://purl.uniprot.org/uniprot/#_D3Z5B0-mappedCitation-27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27111286 |
| http://purl.uniprot.org/uniprot/#_D3Z5S2-mappedCitation-27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27111286 |
| http://purl.uniprot.org/uniprot/#_E9Q6I6-mappedCitation-27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27111286 |
| http://purl.uniprot.org/uniprot/#_A0A1C7ZMZ9-mappedCitation-27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27111286 |
| http://purl.uniprot.org/uniprot/#_P04202-mappedCitation-27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27111286 |
| http://purl.uniprot.org/uniprot/#_P37889-mappedCitation-27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27111286 |
| http://purl.uniprot.org/uniprot/#_Q3UNK5-mappedCitation-27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27111286 |
| http://purl.uniprot.org/uniprot/#_Q3TGL4-mappedCitation-27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27111286 |
| http://purl.uniprot.org/uniprot/#_Q99K58-mappedCitation-27111286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27111286 |