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Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis
dc.contributor.author | Orosa, Beatriz | |
dc.contributor.author | González Martínez-Pedrayo, Antonio | |
dc.contributor.author | Mera Varela, Antonio | |
dc.contributor.author | Gómez-Reino Carnota, Juan Jesús | |
dc.contributor.author | Conde Muro, Carmen | |
dc.date.accessioned | 2023-06-26T07:14:49Z | |
dc.date.available | 2023-06-26T07:14:49Z | |
dc.date.issued | 2012-08 | |
dc.identifier.other | https://pubmed.ncbi.nlm.nih.gov/22354754/ | es |
dc.identifier.uri | http://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.sponsorship | Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (ISCIII) | es |
dc.description.sponsorship | Xunta de Galicia | es |
dc.language.iso | eng | es |
dc.subject.mesh | Apoptosis | * |
dc.subject.mesh | Synoviocytes | * |
dc.subject.mesh | Arthritis, Rheumatoid | * |
dc.subject.mesh | RNA, Messenger | * |
dc.subject.mesh | TNF Receptor-Associated Death Domain Protein | * |
dc.subject.mesh | Blotting, Western | * |
dc.subject.mesh | Receptors, Lysophosphatidic Acid | * |
dc.title | Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis | es |
dc.type | Artigo | es |
dc.identifier.doi | 10.1002/art34443 | |
dc.identifier.pmid | 22354754 | |
dc.issue.number | 8 | es |
dc.journal.title | Arthritis & Rheumatism | es |
dc.organization | Servizo Galego de Saúde::Áreas Sanitarias (A.S.)::Área Sanitaria de Santiago de Compostela - Complexo Hospitalario Universitario de Santiago de Compostela | es |
dc.page.initial | 2460 | es |
dc.page.final | 2470 | es |
dc.relation.projectID | ISCIII/PI08/0038 | es |
dc.relation.projectID | ISCIII/PI11/02197 | es |
dc.relation.projectID | Xunta de Galicia/INCITE08PXIB918235PR | es |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/10.1002/art.34443 | es |
dc.rights.accessRights | openAccess | es |
dc.subject.decs | apoptosis | * |
dc.subject.decs | proteína del dominio de muerte asociada a receptores TNF | * |
dc.subject.decs | inmunotransferencia Western | * |
dc.subject.decs | artritis reumatoide | * |
dc.subject.decs | receptores de ácidos lisofosfatídicos | * |
dc.subject.decs | ARN mensajero | * |
dc.subject.keyword | CHUS | es |
dc.typefides | Artigo Científico (inclue Orixinal, Orixinal breve, Revisión Sistemática e Meta-análisis) | es |
dc.typesophos | Artículo Original | es |
dc.volume.number | 64 | es |