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Analysis of the molecular mechanism in regulation of cell migration by alpha2-plasmin inhibitor

Research Project

Project/Area Number 09470234
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionJichi Medical School, School of Medicine

Principal Investigator

SAKATA Yoichi  Jichi Medical School, School of Medicine, Division of Hemostasis and Thrombosis Research, Associate professor, 医学部, 助教授 (40129028)

Co-Investigator(Kenkyū-buntansha) MADOIWA Seiji  Jichi Medical School, School of Medicine, Division of Hemostasis and Thrombosis, 医学部, 助手 (70296119)
MIMURO Jun  Jichi Medical School, School of Medicine, Division of Hemostasis and Thrombosis, 医学部, 講師 (10221607)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1998: ¥4,700,000 (Direct Cost: ¥4,700,000)
Keywordsplasminogen / alpha2-plasmin inhibitor / angiostatin / fibrin / factor XIII / selectin / α2プラスミンインヒビタ / 血管内皮細胞 / 架橋結合 / プラスミノゲン / 細胞移動 / 組織修復
Research Abstract

Plasminogen (PG) deficient mice result in impaired cell migration and display delayed wound healing. However, fibrinogen deficiency in PG deficient mice corrects healing time. Consequently, these results suggest that the degradation of tissue-fibrin with plasmin (PM) is critical for cell migration. Angiostatin (AST) has been identified as an endogenous inhibitor of neovascularization. In 1998, AST has been shown to inhibit migration and tube formation of endothelial cells. AST, a fragment of PG, contains lysine-binding site (LBS) through which PG and PM bind to fibrin, cell membrane and alpha2-plasmin inhibitor (alpha2-PI). Thereby, we have analyzed the effect of cL2-PI on the PM-mediated cell migration and the inhibitory effect of AST.
1) Analysis of the mechanism of alpha2-PI to participate in tissue fibrinolysis : When fibrinogen or fibrin existed asan extracellular matrix, alpha2-PI was crosslinked to this by factor Xllla. Since alpha2-PI had a high affinity to selectin, we have ana … More lyzed the sugar moiety of alpha2-PI.After degradation with hydrazine and treatment with sialidase, cQ-PI was studied by gyocomap analysis and anion exchange HPLC.Structure of oligosaccharides was deduced by RAMM analysis and the PNA binding. In result, alpha2-PI has N-linked oligosaccharides which has 1-3 sialic acids and 0-linked one containing one sialic acid. In addition, this study has suggested that alpha-Pl contains a sialyl- Lewis x structure.
2) Cell migration studies : The extracellular matrix which contained tibrinogen with crosslinked alpha2-PIattenuated endothelial cell migration. In addition, alpha2-PI delayed migration of endothelial cells, which were stimulated with lipopolysaccharide. Furthermore, alpha2-Pl appeared to neutralize the inhibitory effect of AST on cell migration, whereas a-amino caproic acid did not. Our results with the report that fibroblast growth factor specifically binds to fibrin indicate that alpha2-PI plays an important role in a fine regulation of wound healing. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (57 results)

All Other

All Publications (57 results)

  • [Publications] Sugawara, Y.: "Adenovirus-mediated transfer of tissue-type plasminogen activator gene to human endothelial cells." Surgery. 122(3). 91-100 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Madoiwa, S.: "A battery of monoclonal antibodies that induce unique conformations to evolve cryptic but constitutive functions of plasminogen." J.Biochem.121. 278-287 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Asakura, S.: "Fibroblasts spread on immobilized fibrin monomer by mobilizing a β1-class integrin, together with a vitronectin receptor αvβ3 on their surface." J.Biol.Chem.272(13). 8824-8829 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Funayam, H.: "Monocytes modulates the fibrinolytic balance of endothelial cells." Thromb.Res.85. 377-385 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe, T.: "Successful management of pregnancy in patient with von Willebrand disease Normandy." Obst.& Gynecol.89. 859-860 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuda, T.: "Localization of plasminogen activators and their inhibitor in squamous cell carcinomas of the head and neck." Head & Neck. 64. 611-616 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 坂田 洋一: "血栓形成機序の知識、線溶機構との関連" 日本内科学会雑誌. 86. 889-896 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 坂田 洋一: "血中プラスミノゲンアクチベータインヒビター1測定における諸問題" 血液と腫瘍. 35. 546-552 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 坂田 洋一: "血栓溶解療法" Tokyo Tanabe Quarterly. 41. 198-209 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 静間 奈美: "脳塞栓症にて発症した先天性プロテインC欠乏症の若年成人の1例" 神経治療学. 14. 557-561 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 坂田 洋一: "プラスミノゲンアクチベータインヒビター1、知っておきたい200ワード" 医学の歩み. 181. 830 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuda, T.: "Fibrinolytic components in nasal mucosa and nasal secretion." Histochem.Cell Biol.110. 449-455 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Madoiwa, S.: "Effect of carbohydrate side chain of tissue-type plasminogen activator on its interaction with plasminogen activator inhibitor-1." Fibrinolysis & Proteolysis. 12. 17-22 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Arai, K.: "Role of kringle domain in plasminogen acitvation with staphylokinase." J.Biochem.123. 71-77 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shitaka, M.: "Structural studies of the interaction of normal and abnormal human plasmins with basic pancreatic trypsin inhibitor." Chem.Pharm.Bull.(in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Madoiwa, S.: "Developmental expression of plasminogen activator inhibitor-1 associated with thrombopoietin-dependent megakaryochtic differentiation." Blood. (in press.). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miyata, T.: "Characterization of recombinant human thrombomodulin expressed on human endothelial cells tansduced with adenovirus vector." Thromb.Haemost.(in press.). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mimuro, J.: "A new type of Ser substitution for γ Arg-275 in fibrinogen Kamogawa I characterized by impaired fibrin assembly." Thromb.Haemost.(in press.). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 坂田 洋一: "DICの基礎、線溶とその制御機構、丸山征郎編" メジカルレビュー社, 490 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 坂田 洋一: "新臨床内科学7th ed.高久文麿、尾形悦郎監修、凝固因子欠乏症" 医学書院, 1852 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sugawara, Y.: "Adenovirus-mediated transfer of tissue-type plasminogen activator gene to human endothelial cells." Surgery. 122 (3). 91-100 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Madoiwa, S.: "A battery of monoclonal antibodies that induce unique conformations to evolve cryptic but constitutive functions of plasminogen." J.Biochem.121. 278-287 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Asakura, S.: "Fibroblasts spread on immobilized fibrin monomer by mobilizing a beta1-class integrin, together with a vitronectin receptor alphavbeta3 on their surface." J.Biol.Chem.272.13. 8824-8829 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Funayam, H.: "Monocytes modulates the fibrinolytic balance of endothelial cells." Thromb.Res.85. 377-385 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Watanabe, T.: "Successful management of pregnancy in patient with von Willebrand disease Normandy." Obst.& Gynecol.89. 859-860 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuda, T.: "Localization of plasminogen activators and their inhibitor in squamous cell carcinomas of the head and neck." Head & Neck. 64. 611-616 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuda, T.: "Fibrinolytic components in nasal mucosa and nasal secretion." Histochem.Cell Biol.110. 449-455 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Madoiwa, S.: "Effect of carbohydrate side chain of tissue-type plasminogen activator on its interaction with plasminogen activator inhibitor-1." Fibrinolysis & Proteolysis. 12. 17-22 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Arai, K.: "Role of kringle domain in plasminogen acitvation with staphylokinase." J.Biochem.123. 71-77 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shitaka, M.: "Structural studies of the interaction of normal and abnormal human plasmins with basic pancreatic trypsin inhibitor." Chem.Pharm.Bull.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Madoiwa, S.: "Developmental expression of plasminogen activator inhibitor-1 associated with thrombopoietin-dependent megakaryochtic differentiation." Blood. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miyata, T.: "Characterization of recombinant human thrombomodulin expressed on human endothelial cells transduced with adenovirus vector." Thromb.Haemost.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mimuro, J.: "A new type of Ser substitution for gammaArg-275 in fibrinogen Kamogawa I characterized by impaired fibrin assembly." Thromb.Haemost.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] YASUDA,T: "Fibrinolytic components in nasal mucosa and nasal secretion." Histochem Cell Biol. 110. 449-455 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] ARAI,K: "Role of kringle domain in plasminogen activation with staphylokinase." J Biochem. 123. 71-77 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] MADOIWA,S: "Effect of carbohydrate side chain of tissue-type plasminogen activator on its interaction with plasminogen activator inhibitor-1." Fibrinolysis & Proteolysis. 12. 17-22 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] SHITAKA,M: "Structural studies of the interaction of normal and abnormal human plasmins with basic pancreatic trypsin inhibitor." Chem Pharm Bull,. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] MADOIWA,S: "Developmental expression of plasminogen activator inhibitor-1 associated with thrombopoietin-dependent megakaryochtic differentiation." Blood,. in press.(1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] MIYATA,T: "Characterization of recombinant human thrombomodulin expressed on human endothelial cells transduced with adenovirus vector." Thromb Haemost,. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] MIMURO,J: "A new type of Ser substitution for γArg-275 in fibrinogen Kamogawa I characterized by impaired fibrin assembly." Thromb.Haemost,. in press.(1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 坂田洋一(分担): "造血幹細胞" 南江堂, 272 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] SUGAWARA,Yasuhiko: "Adenovirus-mediated trasnfer of tissue-type plasminogen activator gene to human endothelial cells." Surgery. 122(3). 91-100 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] MADOIWA,Seiji: "A battery of monoclonal antibodies that induce unique conformations to evolve cryptic but constitutive functions of plasminogen." J.Biochem.121. 278-287 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] ASAKURA,Shinji: "Fibroblasts spread on immobilized fibrin monomer by mobilizing a β_1-class integrin,together with a vitronectin receptor αv β3 on their surface." J.Biol.Chem.272(13). 8824-8829 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] FUNAYAMA,Hiroshi: "Monocytes modulates the fibrinolytic balance of endothelial cells." Thromb.Res.85. 377-385 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] WATANABE,Takashi: "Successful management of pregnancy in patient with von Willebrand disease Normandy." Obst.& Gynecol.89. 859-860 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] YASUDA,Toyotoshi: "Localization of plasminogen activators and their inhibitor in squamous cell carcinomas of the head and neck." Head & Neck. 64. 611-616 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] ARAI,Koichi: "Role of the kringle domain in plasminogen activation with staphylokinase." J.Biochem.123. 71-77 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] MADOIWA,Seiji: "Effect of carbohydrate side chain of tissue-type plasminogen activator in interaction with plasminogen activator inhibitor 1." Fibrinolysis & Proteolysis.,in press.

    • Related Report
      1997 Annual Research Report
  • [Publications] MIYATA,Tetsuro: "Characterization of recombinent human thrombomodulin expressed on human endothelial cells transduced with adenovirrus." Circulation,in press.

    • Related Report
      1997 Annual Research Report
  • [Publications] 静間 奈美: "脳塞栓症にて発症した先天性プロテインC欠乏症の若年成人の1例" 神経治療学. 14. 557-561 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 坂田 洋一: "プラスミノゲンアクチベータインヒビター1.知っておきたい200ワード" 医学の歩み. 181. 181- (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 坂田 洋一: "血栓溶解療法" Tokyo Tanabe Quarterly. 41. 198-209 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 坂田 洋一: "血栓形成機序の知識、線溶機構との関連" 日本内科学会雑誌. 86. 889-896 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 坂田 洋一: "血中プラスミノゲンアクチベータインヒビター1測定における諸問題" 血液と腫瘍. 35. 546-552 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 坂田 洋一: "DICの基礎、線溶とその制御機構、丸山征郎編" メジカルレビュー社, 490 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 坂田 洋一: "新臨床内科学7th「高久文麿、尾形悦郎監修」凝固因子欠乏症" 医学書院, 1852 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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