Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis

[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)....

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Detalles Bibliográficos
Autores: Orosa, Beatriz, González Martínez-Pedrayo, Antonio, Mera Varela, Antonio, Gómez-Reino Carnota, Juan Jesús, Conde Muro, Carmen
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/17721
Acceso en línea:https://pubmed.ncbi.nlm.nih.gov/22354754/
http://hdl.handle.net/20.500.11940/17721
Access Level:acceso abierto
Palabra clave:Apoptosis
Synoviocytes
Arthritis, Rheumatoid
RNA, Messenger
TNF Receptor-Associated Death Domain Protein
Blotting, Western
Receptors, Lysophosphatidic Acid
apoptosis
proteína del dominio de muerte asociada a receptores TNF
inmunotransferencia Western
artritis reumatoide
receptores de ácidos lisofosfatídicos
ARN mensajero
CHUS
id ES_de029d885cc6dfc8cabdbbf45d1a86a3
oai_identifier_str oai:runa.sergas.gal:20.500.11940/17721
network_acronym_str ES
network_name_str España
repository_id_str
spelling Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosisOrosa, BeatrizGonzález Martínez-Pedrayo, AntonioMera Varela, AntonioGómez-Reino Carnota, Juan JesúsConde Muro, CarmenApoptosisSynoviocytesArthritis, RheumatoidRNA, MessengerTNF Receptor-Associated Death Domain ProteinBlotting, WesternReceptors, Lysophosphatidic Acidapoptosisproteína del dominio de muerte asociada a receptores TNFinmunotransferencia Westernartritis reumatoidereceptores de ácidos lisofosfatídicosARN mensajeroCHUS[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.Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (ISCIII)Xunta de Galicia2012info:eu-repo/semantics/articlehttps://pubmed.ncbi.nlm.nih.gov/22354754/http://hdl.handle.net/20.500.11940/17721reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Inglésinfo:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/177212026-06-12T08:40:47Z
dc.title.none.fl_str_mv Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis
title Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis
spellingShingle Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis
Orosa, Beatriz
Apoptosis
Synoviocytes
Arthritis, Rheumatoid
RNA, Messenger
TNF Receptor-Associated Death Domain Protein
Blotting, Western
Receptors, Lysophosphatidic Acid
apoptosis
proteína del dominio de muerte asociada a receptores TNF
inmunotransferencia Western
artritis reumatoide
receptores de ácidos lisofosfatídicos
ARN mensajero
CHUS
title_short Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis
title_full Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis
title_fullStr Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis
title_full_unstemmed Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis
title_sort Lysophosphatidic acid receptor 1 suppression sensitizes rheuamatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis
dc.creator.none.fl_str_mv Orosa, Beatriz
González Martínez-Pedrayo, Antonio
Mera Varela, Antonio
Gómez-Reino Carnota, Juan Jesús
Conde Muro, Carmen
author Orosa, Beatriz
author_facet Orosa, Beatriz
González Martínez-Pedrayo, Antonio
Mera Varela, Antonio
Gómez-Reino Carnota, Juan Jesús
Conde Muro, Carmen
author_role author
author2 González Martínez-Pedrayo, Antonio
Mera Varela, Antonio
Gómez-Reino Carnota, Juan Jesús
Conde Muro, Carmen
author2_role author
author
author
author
dc.subject.none.fl_str_mv Apoptosis
Synoviocytes
Arthritis, Rheumatoid
RNA, Messenger
TNF Receptor-Associated Death Domain Protein
Blotting, Western
Receptors, Lysophosphatidic Acid
apoptosis
proteína del dominio de muerte asociada a receptores TNF
inmunotransferencia Western
artritis reumatoide
receptores de ácidos lisofosfatídicos
ARN mensajero
CHUS
topic Apoptosis
Synoviocytes
Arthritis, Rheumatoid
RNA, Messenger
TNF Receptor-Associated Death Domain Protein
Blotting, Western
Receptors, Lysophosphatidic Acid
apoptosis
proteína del dominio de muerte asociada a receptores TNF
inmunotransferencia Western
artritis reumatoide
receptores de ácidos lisofosfatídicos
ARN mensajero
CHUS
description [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.
publishDate 2012
dc.date.none.fl_str_mv 2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://pubmed.ncbi.nlm.nih.gov/22354754/
http://hdl.handle.net/20.500.11940/17721
url https://pubmed.ncbi.nlm.nih.gov/22354754/
http://hdl.handle.net/20.500.11940/17721
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301629

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