ArticleArthritis research & therapy2006
The proinflammatory cytokines IL-1beta and TNF-alpha induce the expression of Synoviolin, an E3 ubiquitin ligase, in mouse synovial fibroblasts via the Erk1/2-ETS1 pathway.
Article in Arthritis research & therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 68 citations in OpenAlex.
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- Effects of α-terpineol and 1,8-cineole fromFrontiers in veterinary science · 2026Article
- Ubiquitination by HRD1 is essential for TLR3 trafficking and its innate immune signaling.Nature communications · 2025Article
- Exploring the ubiquitination regulatory network: opening new perspectives for rheumatoid arthritis therapy.Annals of medicine · 2025Review
- Association between SYVN1 and SEL1 genetic polymorphisms and remission in rheumatoid arthritis patients treated with TNF-α inhibitors: a machine learning approach.Immunologic research · 2023Article
- The noncanonical inflammasome in health and disease.Infectious medicine · 2022Review
- E3 ubiquitin ligase SYVN1 is a key positive regulator for GSDMD-mediated pyroptosis.Cell death & disease · 2022Article
- Interleukin-34-CSF1R Signaling Axis Promotes Epithelial Cell Transformation and Breast Tumorigenesis.International journal of molecular sciences · 2021Article
- Surgical procedures suppress autophagic flux in the kidney.Cell death & disease · 2021Article
- Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis.Journal of inflammation research · 2021Article
- Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Enhanced expression of synoviolin in peripheral blood from obese/overweight donors.Experimental and therapeutic medicine · 2020Article
- Endoplasmic reticulum-associated degradation and beyond: The multitasking roles for HRD1 in immune regulation and autoimmunity.Journal of autoimmunity · 2020Review
- Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis.Frontiers in pharmacology · 2020Article
- ER-localized Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection.Nature microbiology · 2019Article
- Polyphyllin I Ameliorates Collagen-Induced Arthritis by Suppressing the Inflammation Response in Macrophages Through the NF-κB Pathway.Frontiers in immunology · 2018Article
- The Histone Acetyltransferase Gcn5 Positively Regulates T Cell Activation.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Causes and consequences of endoplasmic reticulum stress in rheumatic disease.Nature reviews. Rheumatology · 2017Review
- Bone-protective Functions of Netrin 1 Protein.The Journal of biological chemistry · 2016Article
- Schistosoma japonicum cystatin attenuates murine collagen-induced arthritis.Parasitology research · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The overgrowth of synovial tissues is critical in the pathogenesis of rheumatoid arthritis (RA). The expression of Synoviolin (SYN), an E3 ubiquitin ligase, is upregulated in arthritic synovial fibroblasts and is involved in the overgrowth of synovial cells during RA. However, the molecular mechanisms involved in the elevated SYN expression are not known. Here, we found that SYN expression is elevated in the synovial fibroblasts from mice with collagen-induced arthritis (CIA). The proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha) induce SYN expression in mouse synovial fibroblasts. Cultivation of mouse synovial fibroblasts with IL-1beta activates mitogen-activated protein kinases, including extra-cellular signal-regulated kinase (Erk), JNK (c-Jun N-terminal kinase), and p38, while only Erk-specific inhibitor blocks IL-1beta-induced SYN expression. Expression of transcription factor ETS1 further enhances IL-1beta-induced SYN expression. The dominant negative ETS1 mutant lacking the transcription activation domain inhibits SYN expression in a dose-dependent manner. The activation of both Erk1/2 and ETS1 is increased in the CIA synovial fibroblasts. Inhibition of Erk activation reduces ETS1 phosphorylation and SYN expression. Our data indicate that the proinflammatory cytokines IL-1beta and TNF-alpha induce the overgrowth of synovial cells by upregulating SYN expression via the Erk1/-ETS1 pathway. These molecules or pathways could therefore be potential targets for the treatment of RA.
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