The mechanism how RasGRP4 promotes proliferation of synovial fibroblasts in rheumatoid arthritis
Project/Area Number |
15K09514
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Collagenous pathology/Allergology
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Research Institution | Hokkaido University |
Principal Investigator |
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Project Period (FY) |
2015-10-21 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 関節リウマチ / 線維芽細胞様滑膜細胞 / Ras / RasGRP4 / farnesyltransferase / MAPキナーゼ / TNFα |
Outline of Final Research Achievements |
RasGRP4 is a guanine exchange factor for Ras, expressed mainly in mast cells, monocytes and neutrophils. We previously found aberrant RasGRP4 expression in fibriblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) that controls proliferation of FLS (Kono, Yasuda et al Arthritis Rheumatol 2015). Downstream of RasGRP4, Ras, MAPK activation was confirmed. We investigated the possibility of treatment targeting RasGRP4-Ras-MAPK pathway. Tipifarnib is a farnesyltransferase inhibitor that inhibits Ras activation, mostly tested in clinical trials for neoplasms. Treatment with tipifarnib inhibited FLS proliferation in a dose-dependent manner (Shimamura, Yasuda et al, EAGOR meeting 2017). We suggest inhibition of Ras activation as a feasible treatment for RA).
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Effectiveness of whole-body magnetic resonance imaging for the efficacy of biologic anti-rheumatic drugs in patients with rheumatoid arthritis: a retrospective pilot study2017
Author(s)
Kono M, Kamishima T, Yasuda S, Sakamoto K, Abe S, Noguchi A, Watanabe T, Shimizu Y, Oku K, Bohgaki T, Amengual O, Horita T, Atsumi T
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Journal Title
Mod Rheumatol
Volume: 27
Pages: 953-960
Related Report
Peer Reviewed
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[Journal Article] Clinical Benefit of 1-Year Certolizumab Pegol (CZP) Add-on Therapy to Methotrexate Treatment in Early Rheumatoid Arthritis Patients was Observed Following CZP Discontinuation: 2-Year Results of the C-OPERA Study2017
Author(s)
Atsumi T, Tanaka Y, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Eguchi K, Watanabe A, Origasa H, Yasuda S, Yamanishi Y, Kita Y, Matsubara T, Iwamoto M, Shoji T, Togo O, Okada T, van der Heijde D, Miyasaka N, Koike T
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Journal Title
Ann Rheum Dis
Volume: 76
Issue: 8
Pages: 1348-1356
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Maintenance Treatment using Abatacept with Dose Reduction after Achievement of Low Disease Activity in Patients with Rheumatoid Arthritis (MATADOR) - A prospective, multicenter, single arm pilot clinical trial2017
Author(s)
Yasuda S, Ohmura K, Kanazawa H, Kurita K, Kon Y, Ishii T, Fujieda Y, Jodo S, Tanimura K, Minami M, Izumiyama T, Matsumoto T, Amasaki Y, Suzuki Y, Kasahara H, Yamauchi N, Kato M, Kamishima T, Tsutsumi A, Takemori H, Koike T, Atsumi T
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Journal Title
Mod Rheumatol
Volume: 27
Issue: 6
Pages: 930-937
DOI
Related Report
Peer Reviewed
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[Journal Article] Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes2016
Author(s)
Fujieda Y., Amengual O., Matsumoto M., Kuroki K., Takahashi H., Kono M., Kurita Y., Otomo K., Kato M., Oku K., Bohgaki T., Horita T., Yasuda S., Maenaka K., Hatakeyama S., Nakayama K.I. and Atsumi T. et al.
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Journal Title
Rheumatology
Volume: 印刷中
Issue: 6
Pages: 1117-1126
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Post-steroid neuropsychiatric manifestations are significantly more frequent in SLE compared with other systemic autoimmune diseases and predict better prognosis compared with de novo neuropsychiatric SLE2016
Author(s)
Shimizu Y, Yasuda S, Kato Y, Nakagawa S, Kanda M, Hisada R, Ohmura K, Shimamura S, Shida H, Fujieda Y, Kato M, Oku K, Bohgaki T, Horita T, Kusumi I, Atsumi T
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Journal Title
Autoimmunity Reviews
Volume: Epub ahead
Issue: 8
Pages: 786-794
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Role of apolipoprotein B100 and oxidized low-density lipoprotein in the monocyte tissue factor induction mediated by anti-b2 glycoprotein I antibodies.2016
Author(s)
Otomo K, Amengual O, Fujieda Y, Nakagawa H, Kato M, Oku K, Horita T, Yasuda S, Matsumoto M, Nakayama KI, Hatakeyama S, Koike T, Atsumi T
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Journal Title
Lupus
Volume: Epub ahead
Issue: 12
Pages: 1288-1298
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] AAA-ATPase p97 suppress apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts2016
Author(s)
Kato M, Ospelt C, Kolling C, Shimizu T, Kono M, Yasuda S, Michel BA, Gay RE, Gay S, Klein K, Atsumi T
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Journal Title
Oncotarget
Volume: 7
Pages: 64221-64232
NAID
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression2016
Author(s)
Atsumi T, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka Y, Eguchi K, Watanabe A, Origasa H, Yasuda S, Yamanishi Y, Kita Y, Matsubara T, Iwamoto M, Shoji T, Okada T, van der Heijde D, Miyasaka N, Koike T
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Journal Title
Annals of the Rheumatic Diseases
Volume: 75
Issue: 1
Pages: 75-83
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Assessment of risks for pulmonary infection during 12 months after commencing or intensifying immunosuppressive treatment for active connective tissue diseases: A report from a large-scale prospective cohort study2015
Author(s)
Yamazaki H, Sakai R, Koike R, Miyazaki Y, Tanaka M, Nanki T, Watanabe K, Yasuda S, Kurita T, Kaneko Y, Tanaka Y, Nishioka Y, Takasaki Y, Nagasaka K, Nagasawa H, Tohma S, Dohi M, Sugihara T, Sugiyama H, Kawaguchi Y, Inase N, Ochi S, Hagiyama H, Kohsaka H, Miyasaka N, Harigai M
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Journal Title
Journal of Rheumatology
Volume: 42
Issue: 4
Pages: 614-622
DOI
Related Report
Peer Reviewed
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[Journal Article] Pulmonary infections following immunosuppressive treatment during hospitalization worsen the short-term vital prognosis for patients with connective tissue disease-associated interstitial pneumonia2015
Author(s)
Tanaka M, Koike R, Sakai R, Saito K, Hirata S, Nagasawa H, Kameda H, Hara M, Kawaguchi Y, Tohma S, Takasaki Y, Dohi M, Nishioka Y, Yasuda S, Miyazaki Y, Kaneko Y, Nanki T, Watanabe K, Yamazaki H, Miyasaka N, Harigai M
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Journal Title
Modern Rheumatology
Volume: 25
Issue: 4
Pages: 609-614
DOI
Related Report
Peer Reviewed
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[Journal Article] β2-glycoprotein I/ HLA class II complexes are novel autoantigens in antiphospholipid syndrome.2015
Author(s)
Tanimura K, Jin H, Suenaga T, Morikami S, Arase N, Kishida K, Hirayasu K, Kohyama M, Ebina Y, Yasuda S, Horita T, Takasugi K, Ohmura K, Yamamoto K, Katayama I, Sasazuki T, Lanier LL, Atsumi T, Yamada H, Arase H.
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Journal Title
Blood
Volume: 125
Issue: 18
Pages: 2835-2844
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Surveillance for the use of mycophenolate mofetil for adult patients with lupus nephritis in Japan2015
Author(s)
Yasuda S, Atsumi T, Shimamura S, Ono K, Hiromura K, Sada K, Mori M, Takei S, Kawaguchi Y, Tamura N, Takasaki Y
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Journal Title
Modern Rheumatology
Volume: 25
Issue: 6
Pages: 854-857
DOI
Related Report
Peer Reviewed
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[Journal Article] A national surveillance on current use of mycophenolate mofetil for childhood-onset systemic lupus erythematosus in Japan2015
Author(s)
Hara R, Miyazawa H, Nishimura K, Momoi T, Nozawa T, Kikuchi M, Sakurai N, Kizawa T, Shimamura S, Yasuda S, Hiromura K, Sada K, Kawaguchi Y, Tamura N, Takei S, Takasaki Y, Atsumi T, Mori M
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Journal Title
Modern Rheumatology
Volume: 25
Pages: 858-864
Related Report
Peer Reviewed
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[Presentation] Inhibition of Ras translocation suppresses RasGRP4-induced proliferation of fibroblast-like synoviocytes from patients with rheumatoid arthritis2017
Author(s)
Shimamura S, Yasuda S, Kono M, Shimizu Y, Fujieda Y, Kato M, Oku K, Bohgaki T, Atsumi T
Organizer
EAGOR meeting, Tokyo, Japan
Related Report