دورية أكاديمية
Implication of the deacetylase sirtuin-1 on synovial angiogenesis and persistence of experimental arthritis
| العنوان: | Implication of the deacetylase sirtuin-1 on synovial angiogenesis and persistence of experimental arthritis |
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| المؤلفون: | Leblond, Agathe, Pezet, Sonia, Cauvet, Anne, Casas, Claudine, Pires da Silva, Julie, Hervé, Roxane, Clavel, Gaëlle, Dumas, Sébastien J., Cohen-Kaminsky, Sylvia, Bessis, Natacha, Semerano, Luca, Lemaire, Christophe, Allanore, Yannick, Avouac, Jérôme |
| المساهمون: | Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Cochin Departement Infection, immunité, inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Signalisation et physiopathologie cardiovasculaire (CARPAT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Physiopathologie, cibles et thérapies de la polyarthrite rhumatoïde (Li2P), Université Sorbonne Paris Cité (USPC)-UFR Santé, Médecine et Biologie Humaine-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Fondation Ophtalmologique Adolphe de Rotschild, Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Université Paris-Saclay, Faculté de Médecine, 94270 Le Kremlin-Bicêtre, France, AP-HP - Hôpital Cochin Broca Hôtel Dieu Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UFR Médecine Santé - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Pfizer, Funding This study was funded by société Française de rhumatologie, arthritis r&D, Bourse Passerelle (Pfizer). |
| المصدر: | ISSN: 0003-4967. |
| بيانات النشر: | HAL CCSD BMJ Publishing Group |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | arthritis, experimental, rheumatoid, synovitis, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Objectives To decipher the phenotype of endothelial cells (ECs) derived from circulating progenitors issued from patients with rheumatoid arthritis (RA). Methods RA and control ECs were compared according to their proliferative capacities, apoptotic profile, response to tumour necrosis factor (TNF)-α stimulation and angiogenic properties. Microarray experiments were performed to identify gene candidates relevant to pathological angiogenesis. Identified candidates were detected by RT-PCR and western blot analysis in ECs and by immunohistochemistry in the synovium. Their functional relevance was then evaluated in vitro after gene invalidation by small interfering RNA and adenoviral gene overexpression, and in vivo in the mouse model of methyl-bovine serum albumin-(mBSA)-induced arthritis. Results RA ECs displayed higher proliferation rate, greater sensitisation to TNF-α and enhanced in vitro and in vivo angiogenic capacities. Microarray analyses identified the NAD-dependent protein deacetylase sirtuin-1 (SIRT1) as a relevant gene candidate. Decreased SIRT1 expression was detected in RA ECs and synovial vessels. Deficient endothelial SIRT1 expression promoted a proliferative, proapoptotic and activated state of ECs through the acetylation of p53 and p65, and lead the development of proangiogenic capacities through the upregulation of the matricellular protein cysteine-rich angiogenic protein-61. Conditional deletion of SIRT1 in ECs delayed the resolution of experimental methyl-bovine serum albumin-(mBSA)-induced arthritis. Conversely, SIRT1 activation reversed the pathological phenotype of RA ECs and alleviates signs of experimental mBSA-induced arthritis. Conclusions These results support a role of SIRT1 in RA and may have therapeutic implications, since targeting angiogenesis, and especially SIRT1, might be used as a complementary therapeutic approach in RA. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32381568; hal-02927538; https://hal.science/hal-02927538Test; PUBMED: 32381568 |
| DOI: | 10.1136/annrheumdis-2020-217377 |
| الإتاحة: | https://doi.org/10.1136/annrheumdis-2020-217377Test https://hal.science/hal-02927538Test |
| رقم الانضمام: | edsbas.EA907955 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/annrheumdis-2020-217377 |
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