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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• 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 / 血栓症

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
  • Journal Title: Rheumatol Int Volume: (in press)
  • Peer Reviewed
• [Journal Article] Long-term outcome in Japanese patients with lupus nephritis (2014)
  • Author(s): Kono M, Yasuda S, Kato M, Kanetsuka Y, Kurita T, Fujieda Y, Otomo K, Horita T, Oba K, Kondo M, Mukai M, Yanai M, Fukasawa Y, Atsumi T
  • 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
  • Journal Title: Rheumatology (Oxford) Volume: (in press)
  • Peer Reviewed
• [Journal Article] Decreased expression of Runx1 and lowered production of Foxp3+ CD25+ CD4+ regulatory T cells in systemic sclerosis (2014)
  • Author(s): Kataoka H, Yasuda S, Fukaya S, Oku K, Horita T, Atsumi T, Koike T
  • Journal Title: Mod Rheumatol Volume: (in press)
  • Peer Reviewed
• [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)
  • Peer Reviewed
• [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)
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Decreased expression of Runx1 and lowered production of Foxp3+ CD25+ CD4+ regulatory T cells in systemic sclerosis (2014)
  • Author(s): Kataoka H, Yasuda S, Fukaya S, Oku K, Horita T, Atsumi T, Koike T
  • Journal Title: Modern Rheumatology Volume: 未定
  • Peer Reviewed
• [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: Rheumatology International Volume: 未定
  • Peer Reviewed
• [Journal Article] 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: Modern Rheumatology Volume: 未定
  • Peer Reviewed
• [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: Proceedings of National Academy of Science USA Volume: 111 Issue: 10 Pages: 3787-3792
  • DOI: 10.1073/pnas.1401105111
  • Peer Reviewed / Open Access
• [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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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
  • NAID: 130003365862
  • Peer Reviewed
• [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
  • NAID: 10031167669
  • Peer Reviewed
• [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: In press
  • NAID: 130003365862
  • Peer Reviewed
• [Journal Article] Essential role of the p38 mitogen-activated protein kinase pathway in tissue factor gene expression mediated by the phosphatidylserine-dependent antiprothrombin antibody (2013)
  • Author(s): Oku K, Amengual O, Zigon P, Horita T, Yasuda S, Atsumi T
  • Journal Title: rheumatology (Oxford) Volume: In press
  • Peer Reviewed
• [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
  • NAID: 120005356853
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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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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 Pages: 1765-74
  • Peer Reviewed
• [Journal Article] Predominant prevalence of arterial thrombosis in Japanese patients with antiphospholipid (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: syndromeLupus Volume: 21(14) Issue: 14 Pages: 1506-14
  • DOI: 10.1177/0961203312458469
  • Peer Reviewed
• [Journal Article] Phospholipid scramblase 1 expression is enhanced in patients with antiphospholipid syndrome (2012)
  • Author(s): Amengual O, Atsumi T, Oku K, Suzuki E, Horita T, Yasuda S, Koike T
  • Journal Title: Mod Rheumatol Volume: 23(1) Issue: 1 Pages: 81-8
  • DOI: 10.1007/s10165-012-0642-9
  • NAID: 10031167669
  • Peer Reviewed
• [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 Issue: 2 Pages: 504-512
  • DOI: 10.1002/art.33340
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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)
  • NAID: 120003945421
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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
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• [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
  • NAID: 10029513170
  • Peer Reviewed
• [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 Issue: 5
  • DOI: 10.1186/ar3470
  • NAID: 120003945421
  • Peer Reviewed
• [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 Issue: 10 Pages: 2209-2214
  • DOI: 10.3899/jrheum.110289
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• [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 Issue: 10 Pages: 1047-1056
  • DOI: 10.1177/0961203311403347
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• [Journal Article] Clinical features of reversible posterior leukoencephalopathy syndrome in patients with systemic lupus erythematosus. (2011)
  • Author(s): Fujieda Y, Kataoka H, Odani T, Otomo K, Kato M, Fukaya S, Oku K, Horita T, Yasuda S, Atsumi T, Koike T.
  • Journal Title: Mod Rheumatol Volume: 21 Issue: 3 Pages: 276-281
  • DOI: 10.1007/s10165-010-0386-3
  • 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 Issue: 4 Pages: 444-448
  • DOI: 10.1007/s10165-011-0421-z
  • NAID: 10029513170
  • Peer Reviewed
• [Presentation] 強皮症に対する造血幹細胞移植 (2014)
  • Author(s): 保田晋助
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都）
• [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
• [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
  • Place of Presentation: Novotel Budapest City, Budapest, Hungary
• [Presentation] 関節リウマチにおけるRasGRP4の発現異常 (2013)
  • Author(s): 保田晋助
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 京都国際会議場（京都市）
• [Presentation] Role of β2-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
  • Place of Presentation: ノボテルブダペストシティ、ブダペスト（ハンガリー）
• [Presentation] Diagnosis and treatment of RA in Japan (2013)
  • Author(s): Yasuda S
  • Organizer: The 6th Rheumatology Meeting in Aubrac
  • Place of Presentation: ベストウエスタンラギオール、オーブラック（フランス）
  • Invited
• [Presentation] Role of b2-glycoprotein I and b2-glycoprotein I domain V in angiogenesis (2013)
  • Author(s): Yasuda S, Kubota A, Nakagawa H, Kuroki K, Fujieda Y, Oku K, Bohgaki T, Amengual O, Horita T, Maenaka K, Atsumi T
  • Organizer: Controversies in Rheumatology and Autoimmunity
  • Place of Presentation: ノボテルブダペストシティ（ハンガリー）
• [Presentation] IL-6 rationale in RA–from bench side (2012)
  • Author(s): Yasuda S
  • Organizer: AURORA meeting
  • Place of Presentation: London, UK
• [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
• [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
• [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: 5th Asian congress on autoimmunity
  • Place of Presentation: Congress Venue (Singapore)
• [Presentation] HLA-DRB5* 01:05 as a risk for systemic sclerosis and scleroderma-related interstitial lung disease (2011)
  • Author(s): Yasuda S, Odani T, Otomo K, Kato M, Horita T, Atsumi T, Koike T
  • Organizer: 2011日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ (千葉)
• [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)
• [Book] 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
  • Publisher: 医歯薬出版株式会社
• [Book] 顕微鏡的多発血管炎 (2012)
  • Author(s): 保田 晋助
  • Publisher: 医薬ジャーナル社
• [Remarks]
  • URL: http://www.hucc.hokudai.ac.jp/
• [Remarks] 北海道大学大学院医学研究科 内科学講座 免疫・代謝内科学分野
  • URL: http://www.hucc.hokudai.ac.jp/