دورية أكاديمية
أعرض في EDS

Cyld restrains the hyperactivation of synovial fibroblasts in inflammatory arthritis by regulating the TAK1/IKK2 signaling axis.

التفاصيل البيبلوغرافية
العنوان: Cyld restrains the hyperactivation of synovial fibroblasts in inflammatory arthritis by regulating the TAK1/IKK2 signaling axis.
المؤلفون: Rinotas V; Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center (BSRC) 'Alexander Fleming', Vari, Greece., Iliaki K; Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center (BSRC) 'Alexander Fleming', Vari, Greece., Pavlidi L; Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center (BSRC) 'Alexander Fleming', Vari, Greece., Meletakos T; Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center (BSRC) 'Alexander Fleming', Vari, Greece., Mosialos G; School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece., Armaka M; Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center (BSRC) 'Alexander Fleming', Vari, Greece. armaka@fleming.gr.
المصدر: Cell death & disease [Cell Death Dis] 2024 Aug 09; Vol. 15 (8), pp. 584. Date of Electronic Publication: 2024 Aug 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101524092 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-4889 (Electronic) NLM ISO Abbreviation: Cell Death Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Pub. Group
مواضيع طبية MeSH: Fibroblasts*/metabolism , Fibroblasts*/pathology , Deubiquitinating Enzyme CYLD*/metabolism , Deubiquitinating Enzyme CYLD*/genetics , MAP Kinase Kinase Kinases*/metabolism , MAP Kinase Kinase Kinases*/genetics , Signal Transduction* , Synovial Membrane*/metabolism , Synovial Membrane*/pathology , I-kappa B Kinase*/metabolism , I-kappa B Kinase*/genetics , Arthritis, Rheumatoid*/metabolism , Arthritis, Rheumatoid*/pathology , Arthritis, Rheumatoid*/genetics, Animals ; Mice ; Tumor Necrosis Factor-alpha/metabolism ; Tumor Necrosis Factor-alpha/pharmacology ; Humans ; NF-kappa B/metabolism ; Mice, Inbred C57BL ; Mice, Knockout
مستخلص: TNF is a potent cytokine known for its involvement in physiology and pathology. In Rheumatoid Arthritis (RA), persistent TNF signals cause aberrant activation of synovial fibroblasts (SFs), the resident cells crucially involved in the inflammatory and destructive responses of the affected synovial membrane. However, the molecular switches that control the pathogenic activation of SFs remain poorly defined. Cyld is a major component of deubiquitination (DUB) machinery regulating the signaling responses towards survival/inflammation and programmed necrosis that induced by cytokines, growth factors and microbial products. Herein, we follow functional genetic approaches to understand how Cyld affects arthritogenic TNF signaling in SFs. We demonstrate that in spontaneous and induced RA models, SF-Cyld DUB deficiency deteriorates arthritic phenotypes due to increased levels of chemokines, adhesion receptors and bone-degrading enzymes generated by mutant SFs. Mechanistically, Cyld serves to restrict the TNF-induced hyperactivation of SFs by limiting Tak1-mediated signaling, and, therefore, leading to supervised NF-κB and JNK activity. However, Cyld is not critically involved in the regulation of TNF-induced death of SFs. Our results identify SF-Cyld as a regulator of TNF-mediated arthritis and inform the signaling landscape underpinning the SF responses.
(© 2024. The Author(s).)
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المشرفين على المادة: EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
EC 2.7.11.25 (MAP kinase kinase kinase 7)
EC 2.7.11.25 (MAP Kinase Kinase Kinases)
EC 3.4.19.12 (CYLD protein, mouse)
EC 2.7.11.10 (I-kappa B Kinase)
0 (Tumor Necrosis Factor-alpha)
0 (NF-kappa B)
تواريخ الأحداث: Date Created: 20240809 Date Completed: 20240809 Latest Revision: 20240821
رمز التحديث: 20240822
مُعرف محوري في PubMed: PMC11316070
DOI: 10.1038/s41419-024-06966-2
PMID: 39122678
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-4889
DOI:10.1038/s41419-024-06966-2