Role of recombinant nicked beta2-glycoprotein I domain V in angiogenesis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591431
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Hokkaido University
• Principal Investigator: YASUDA Shinsuke 北海道大学, 医学(系)研究科(研究院), 講師 (00374231)
• Project Period (FY): 2011 – 2013
• Keywords: 血管新生 / アンギオスタチン / β2-グリコプロテインI / 抗リン脂質抗体症候群

Research Abstract

Previously we reported nicked beta2-glycoprotein I (b2GPI) binds to angiostatin via its domain V and exerts pro-angiogenic effect (Nakagawa et al. Blood 2009). The aim of this study was to investigate the role of b2GPI domain V in angiogenesis. Recombinant b2GPI domain V was generated in mammalian cell expression system and bacteria. Purification of the product was done using anti-FLAG column or nickel column. Binding between intact/nicked b2GPI domain V and angiostatin 4.5 (AS4.5) was evaluated using surface plasmon resonance. Nicked b2GPI domain V specifically bound onto AS4.5 at KD of ~ 5 x 10-8M, whereas intact b2GPI domain V showed no specific binding. Cell proliferation assay using human umbilical endothelial cells (HUVECs) were performed in the presence or absence of intact/nicked b2GPI domain V. Both intact and nicked b2GPI domain V slightly inhibited cell proliferation at 0.4uM.
In conclusion, nicked b2GPI domain V bound to AS4.5, as observed in nicked form of whole b2GPI.

Research Products

• [Journal Article] The risk of serious infection in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors decreased over time; a report from the registry of Japanese rheumatoid arthritis patients for long-term safety (REAL) database (2014)
  • Author(s): Sakai R, Cho SK, Nanki T, Koike R, Watanabe K, Yamazaki H, Nagasawa H, Amano K, Tanaka Y, Sumida T, Ihata A, Yasuda S, Nakajima A, Sugihara T, Tamura N, Fujii T, Dobashi H, Miura Y, Miyasaka N, Harigai M
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  • Journal Title: Lupus Volume: (in press)
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• [Journal Article] The effect of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis (2014)
  • Author(s): Kurita T, Yasuda S, Oba K, Odani T, Kono M, Otomo K, Fujieda Y, Oku K, Bohgaki T, Amenguak O, Horita T, Atsumi T
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• [Journal Article] Decreased expression of Runx1 and lowered production of Foxp3+ CD25+ CD4+ regulatory T cells in systemic sclerosis (2014)
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  • Journal Title: Mod Rheumatol Volume: (in press)
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• [Journal Article] Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiphospholipid antibodies (2014)
  • Author(s): Amengual O, Horita T, Binder W, Norman GL, Shums Z, Kato M, Otomo K, Fujieda Y, Oku K, Bohgaki T, Yasuda S, Atsumi T
  • Journal Title: Rheumatol Int Volume: (in press)
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• [Journal Article] for the RESEARCH investigators; the REAL Study Group. A comparison of incidence and risk factors for serious adverse events in rheumatoid arthritis patients with etanercept or adalimumab in Korea and Japan (2014)
  • Author(s): Cho SK, Sakai R, Nanki T, Koike R, Watanabe K, Yamazaki H, Nagasawa H, Tanaka Y, Nakajima A, Yasuda S, Ihata A, Ezawa K, Won S, Choi CB, Sung YK, Kim TH, Jun JB, Yoo DH, Miyasaka N, Bae SC, Harigai M
  • Journal Title: Mod Rheumatol Volume: (in press)
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• [Journal Article] Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility (2014)
  • Author(s): Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H
  • Journal Title: Proc Natl Acad Sci USA Volume: 111(10) Pages: 3787-92
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• [Journal Article] Essential role of p38 mitogen-activated protein kinase pathway in tissue factor gene expression mediated by the phosphatidylserina-dependent antiprothrombin antibody (2013)
  • Author(s): Oku K, Amengual O, Zigon P, Horita T, Yasuda S, Atsumi T
  • Journal Title: Rheumatology (Oxford) Volume: 52(10) Pages: 1775-84
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• [Journal Article] The involvement of CD36 in monocyte activation by antiphospholipid antibodies (2013)
  • Author(s): Kato M, Atsumi T, Oku K, Amengual O, Nakagawa H, Fujieda Y, Otomo K, Horita T, Yasuda S, Koike T
  • Journal Title: Lupus Volume: 22(8) Pages: 761-71
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• [Journal Article] Disseminated intravascular coagulation in the presence of antiphospholipid antibodies : differential diagnosis from catastrophic or microangiopathic antiphospholipid syndrome (2013)
  • Author(s): Yasuda S
  • Journal Title: Intern Med Volume: 52(2) Pages: 169-70
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• [Journal Article] Phospholipid scramblase 1 expression is enhanced in patients with antiphospholipid syndrome (2013)
  • Author(s): Amengual O, Atsumi T, Oku K, Suzuki E, Horita T, Yasuda S, Koike T
  • Journal Title: Mod Rheumatol Volume: 23(1) Pages: 81-8
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• [Journal Article] Predominant prevalence of arterial thrombosis in Japanese patients with the antiphospholipid syndrome (2012)
  • Author(s): Fujieda Y, Atsumi T, Amengual O, Odani T, Otomo K, Kato M, Oku K, Kon Y, Horita T, Yasuda S, Koike T
  • Journal Title: Lupus Volume: 21(14) Pages: 1506-14
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• [Journal Article] Up-regulated expression of HLA-DRB5 transcripts and high frequency of the HLA-DRB5*01:05 allele in scleroderma patients with interstitial lung disease (2012)
  • Author(s): Odani T, Yasuda S, Ota Y, Fujieda Y, Kon Y, Horita T, Kawaguchi Y, Atsumi T, Yamanaka H, Koike T
  • Journal Title: Rheumatology (Oxford) Volume: 51(10) Pages: 1765-74
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• [Journal Article] The efficacy of antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events (2012)
  • Author(s): Otomo K, Atsumi T, Amengual O, Fujieda Y, Kato M, Oku K, Horita T, Yasuda S, Koike T
  • Journal Title: Arthritis Rheum Volume: 64(2) Pages: 504-12
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• [Journal Article] Aberrant splicing of the hRasGRP4 transcript and decreased levels of this signaling protein in the peripheral blood mononuclear cells in a subset of patients with rheumatoid arthritis (2011)
  • Author(s): Hashimoto T, Yasuda S, Koide H, Kataoka H, Horita T, Atsumi T, Koike T
  • Journal Title: Arthritis Res Ther Volume: 13(5) Pages: R154
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• [Journal Article] Hepatitis B virus reactivation by immunosuppressive therapy in patients with autoimmune diseases : Risk analysis in hepatitis B surface antigen-negative cases (2011)
  • Author(s): Kato M, Atsumi T, Kurita T, Odani T, Fujieda Y, Otomo K, Horita T, Yasuda S, Koike T
  • Journal Title: J Rheumatol Volume: 38(10) Pages: 2209-14
  • Peer Reviewed
• [Journal Article] The short-term role of corticosteroid therapy for pulmonary arterial hypertension associated with connective tissue diseases : report of five cases and a literatural review (2011)
  • Author(s): Kato M, Kataoka H, Odani T, Fujieda Y, Otomo K, Oku K, Horita T, Yasuda S, Atsumi T, Tsujino I, Nishimura M, Koike T
  • Journal Title: Lupus Volume: 20(10) Pages: 1047-56
  • Peer Reviewed
• [Journal Article] The REAL database reveals no significant risk of serious infection during treatment with a methotrexate dose of more than 8 mg/week in patients with rheumatoid arthritis (2011)
  • Author(s): Sakai R, Komano Y, Tanaka M, Nanki T, Koike R, Nakajima A, Atsumi T, Yasuda S, Tanaka Y, Saito K, Tohma S, Fujii T, Ihata A, Tamura N, Kawakami A, Sugihara T, Ito S, Miyasaka N, Harigai M
  • Journal Title: Mod Rheumatol Volume: 21(4) Pages: 444-8
  • Peer Reviewed
• [Presentation] Diagnosis and treatment of RA in Japan, Experience and recommendations of using Tocilizumab in general (2013)
  • Author(s): Yasuda S
  • Organizer: The 6th Rheumatology Meeting in Aubrac
  • Place of Presentation: Best Western Lagiore, Aubrac, France
  • Year and Date: 20130611-12
• [Presentation] Role ofβ_2-glycoprotein I Domain V in Angiogenesis (2013)
  • Author(s): Yasuda S, Kubota A, Nakagawa H, Kuroki K, Fujieda Y, Bohgaki T, Amengual O, Horita T, Maenaka K, Atsumi T
  • Organizer: CORA meeting
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  • Year and Date: 20130404-06
• [Presentation] IL-6 rationale in RA–from bench side (2012)
  • Author(s): Yasuda S
  • Organizer: AURORA meeting
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• [Presentation] Haematopoietic stem cell transplantation for interstitial lung diseases in patients with systemic sclerosis; Therapeutic effect and evaluation of up-regulated genes (2012)
  • Author(s): Yasuda S, Odani T, Ota Y, Fujieda Y, Kon Y, Horita T, Kawaguchi Y, Atsumi T, Yamanaka H, Koike T
  • Organizer: The 8^<th> international congress on autoimmunity
  • Place of Presentation: Palacio de Exposiciones y Congresos de Granada, Granada, Spain
  • Year and Date: 20120509-13
• [Presentation] Aberrant expression of Mx1 in T cells from patients with systemic lupus erythematosus (2011)
  • Author(s): Yasuda S, Kono M, Horita T, Atsumi T, Koike T
  • Organizer: 5^<th> Asian congress on autoimmunity
  • Place of Presentation: Singapore
  • Year and Date: 20111117-19
• [Book] 全身性エリテマトーデスに対する抗体治療–分子標的治療開発の道のりと現状, 別冊医学のあゆみ,抗体医薬Update–開発コンセプトから最新治療実績まで (2012)
  • Author(s): 保田晋助,小池隆夫, (中山俊憲・中島裕史編)
  • Total Pages: 146
  • Publisher: 医歯薬出版株式会社, (東京都)
• [Book] 顕微鏡的多発血管炎, 膠原病の肺合併症診療マニュアル (2012)
  • Author(s): 保田晋助, (宮坂信之編)
  • Total Pages: 207
  • Publisher: 医薬ジャーナル社, (大阪市)
• [Remarks]
  • URL: http://www.hucc.hokudai.ac.jp/