| http://purl.uniprot.org/citations/24956016 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24956016 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations affecting transforming growth factor-beta (TGF-β) superfamily receptors, activin receptor-like kinase (ALK)-1, and endoglin (ENG) occur in patients with pulmonary arterial hypertension (PAH). To determine whether the TGF-β/ALK1/ENG pathway was involved in PAH, we investigated pulmonary TGF-β, ALK1, ALK5, and ENG expressions in human lung tissue and cultured pulmonary-artery smooth-muscle-cells (PA-SMCs) and pulmonary endothelial cells (PECs) from 14 patients with idiopathic PAH (iPAH) and 15 controls. Seeing that ENG was highly expressed in PEC, we assessed the effects of TGF-β on Smad1/5/8 and Smad2/3 activation and on growth factor production by the cells. Finally, we studied the consequence of ENG deficiency on the chronic hypoxic-PH development by measuring right ventricular (RV) systolic pressure (RVSP), RV hypertrophy, and pulmonary arteriolar remodeling in ENG-deficient (Eng+/-) and wild-type (Eng+/+) mice. We also evaluated the pulmonary blood vessel density, macrophage infiltration, and cytokine expression in the lungs of the animals. Compared to controls, iPAH patients had higher serum and pulmonary TGF-β levels and increased ALK1 and ENG expressions in lung tissue, predominantly in PECs. Incubation of the cells with TGF-β led to Smad1/5/8 phosphorylation and to a production of FGF2, PDGFb and endothelin-inducing PA-SMC growth. Endoglin deficiency protected mice from hypoxic PH. As compared to wild-type, Eng+/-mice had a lower pulmonary vessel density, and no change in macrophage infiltration after exposure to chronic hypoxia despite the higher pulmonary expressions of interleukin-6 and monocyte chemoattractant protein-1. The TGF-β/ALK1/ENG signaling pathway plays a key role in iPAH and experimental hypoxic PH via a direct effect on PECs leading to production of growth factors and inflammatory cytokines involved in the pathogenesis of PAH."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0100310"xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Humbert M."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Simonneau G."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Dewachter L."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Fadel E."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Eddahibi S."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Izikki M."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Dartevelle P."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Lebrin F."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Naeije R."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Gore B."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/author | "Mercier O."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/pages | "e100310"xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/title | "Key role of the endothelial TGF-beta/ALK1/endoglin signaling pathway in humans and rodents pulmonary hypertension."xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://purl.uniprot.org/core/volume | "9"xsd:string |
| http://purl.uniprot.org/citations/24956016 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24956016 |
| http://purl.uniprot.org/citations/24956016 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24956016 |
| http://purl.uniprot.org/uniprot/#_D3Z7H9-mappedCitation-24956016 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24956016 |
| http://purl.uniprot.org/uniprot/#_E9Q6I6-mappedCitation-24956016 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24956016 |
| http://purl.uniprot.org/uniprot/#_F7BZW0-mappedCitation-24956016 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24956016 |
| http://purl.uniprot.org/uniprot/#_A9Z1A0-mappedCitation-24956016 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24956016 |