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dc.contributor.authorOrosa, Beatriz
dc.contributor.authorGonzález Martínez-Pedrayo, Antonio 
dc.contributor.authorMera Varela, Antonio 
dc.contributor.authorGómez-Reino Carnota, Juan Jesús 
dc.contributor.authorConde Muro, Carmen 
dc.date.accessioned2023-06-26T07:14:49Z
dc.date.available2023-06-26T07:14:49Z
dc.date.issued2012-08
dc.identifier.otherhttps://pubmed.ncbi.nlm.nih.gov/22354754/es
dc.identifier.urihttp://hdl.handle.net/20.500.11940/17721
dc.description.abstract[EN] Objective. To investigate the role of lysophosphatidic acid (LPA) receptors in the proliferation and apoptosis of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Methods. Expression of LPA receptors 1–3 was analyzed by real-time polymerase chain reaction (PCR). LPAR1 and LPAR2 were suppressed in RA FLS by small interfering RNA (siRNA) transfection. Proliferation of RA FLS after tumor necrosis factor (TNF) and LPA stimulation was determined with a luminescent cell viability assay. Apoptosis was analyzed by quantification of nucleosome release and measurement of activated caspase 3/7. Genes involved in the apoptotic response were identified with a human apoptosis PCR array and validated with Western blot assays. The requirement of these genes for apoptosis sensitization was assessed by siRNA transfection. Secretion of mediators of inflammation was analyzed by enzyme-linked immunosorbent assay. Results. Only LPAR1 and LPAR2 were expressed by RA FLS, and their levels were higher than those in osteoarthritis (OA) FLS. Suppression of LPAR1 abrogated TNF-induced proliferation and sensitized the RA FLS, but not the OA FLS, to TNF-induced apoptosis. These changes occurred despite an increased early inflammatory response to TNF. Sensitization to apoptosis was associated with changes in expression of multiple apoptosis-related genes. Three of the up-regulated proapoptotic genes were further studied to confirm their involvement. In contrast, suppression of LPAR2 showed no effect in any of these analyses. Conclusion. LPA1 is an important receptor in RA FLS. Its suppression is accompanied by a global increase in the response to TNF that is ultimately dominated by sensitization to apoptosis.es
dc.description.sponsorshipFondo de Investigación Sanitaria del Instituto de Salud Carlos III (ISCIII)es
dc.description.sponsorshipXunta de Galiciaes
dc.language.isoenges
dc.subject.meshApoptosis*
dc.subject.meshSynoviocytes*
dc.subject.meshArthritis, Rheumatoid*
dc.subject.meshRNA, Messenger*
dc.subject.meshTNF Receptor-Associated Death Domain Protein*
dc.subject.meshBlotting, Western*
dc.subject.meshReceptors, Lysophosphatidic Acid*
dc.titleLysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosises
dc.typeArtigoes
dc.identifier.doi10.1002/art34443
dc.identifier.pmid22354754
dc.issue.number8es
dc.journal.titleArthritis & Rheumatismes
dc.organizationServizo Galego de Saúde::Áreas Sanitarias (A.S.)::Área Sanitaria de Santiago de Compostela - Complexo Hospitalario Universitario de Santiago de Compostelaes
dc.page.initial2460es
dc.page.final2470es
dc.relation.projectIDISCIII/PI08/0038es
dc.relation.projectIDISCIII/PI11/02197es
dc.relation.projectIDXunta de Galicia/INCITE08PXIB918235PRes
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/10.1002/art.34443es
dc.rights.accessRightsopenAccesses
dc.subject.decsapoptosis*
dc.subject.decsproteína del dominio de muerte asociada a receptores TNF*
dc.subject.decsinmunotransferencia Western*
dc.subject.decsartritis reumatoide*
dc.subject.decsreceptores de ácidos lisofosfatídicos*
dc.subject.decsARN mensajero*
dc.subject.keywordCHUSes
dc.typefidesArtigo Científico (inclue Orixinal, Orixinal breve, Revisión Sistemática e Meta-análisis)es
dc.typesophosArtículo Originales
dc.volume.number64es


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