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Investigation of mechanism of pulmonary fibrosis focusing on post-translational modification of osteopontin and its receptor change

Research Project

Project/Area Number 18590853
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHiroshima University

Principal Investigator

YOKOSAKI Yasuyuki  Hiroshima University, Health Service Center, Associate Professor (80210607)

Co-Investigator(Kenkyū-buntansha) NAKATA Koh  Niigata University, Medical and Dental Hospital, Professor (80207802)
MORIMOTO Yasuo  Hiroshima University, University of Occupational and Environmental Health, Institute of Industrial Ecological Science, Professor (30258628)
YAMASHITA Keisuke  Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (40166666)
HIGASHIKAWA Fumiko  Hiroshima University, Funiko Graduate School of Biomedical Sciences, Associate Professor (70346534)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsPulmonary Fibrosis / Osteopontin / Integrin / Neutrophil / Chemoattractant / トランスグルタミナーゼ / 重合
Research Abstract

We investigated mechanism of pulmonary fibrosis focusing on post-translational modifications of osteopontin and associating receptor change.
1) Osteopontin was polymerized by transglutaminase 2.
2) Cell adhesion, spreading, and migration were enhanced when cells were plated on polymeric osteopontin than on monomeric osteopontin.
3) Focal contact formation in cells plated on polymeric osteopontin was dramatic, which suggests the cell behaviors described above were mediated by integrin receptors.
4) Polymeric osteopontin induces neutrophil migration in vitro, which was analyzed by horizontal migration analysis apparatus, Taxiscan.
5) Polymeric osteopontin recruited neutrophils into mouse peritoneal space.
These results suggest that polymerization of osteopontin is involved in lung injury induced by neutrophils, the first step of pulmonary fibrosis. Although we could not describe in this report, we are on a process of generating osteopontin mutant mice to confirm the effects of polymerization of osteopontin on pulmonary fibrosis.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (17 results)

All 2008 2007 Other

All Journal Article (10 results) (of which Peer Reviewed: 6 results) Presentation (7 results)

  • [Journal Article] Gene-environment association of an ITGB2 sequence variant with obesity in Ethnic Japanese2008

    • Author(s)
      Awaya T, et. al.
    • Journal Title

      Obesity 16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gene-environment association of an ITGB2 sequence variant with obesity in ethnic Japanese2008

    • Author(s)
      Awaya, T., et. al.
    • Journal Title

      Obesity 16

      Pages: 1463-1466

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gene-Environment association of an ITGB2 sequence variant with obesity in ethnic Japanese2008

    • Author(s)
      Awaya, T
    • Journal Title

      Obesity (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced biological activity of polymeric osteopontin.2007

    • Author(s)
      Higashikawa F, et. al.
    • Journal Title

      FEBS letters 581

      Pages: 2697-2701

    • NAID

      120000875265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The integrin α5β1 regulates chondrocyte hypertrophic differentiation induced by GTP-bound transglutaminase 22007

    • Author(s)
      Tanaka K, et. al.
    • Journal Title

      Matrix Biol 26

      Pages: 409-418

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The integrin α5β1 regulates chondrocyte hypertrophic differentiation induced by GTP-bound transglutaminase 22007

    • Author(s)
      Tanaka, K., et. al.
    • Journal Title

      Matrix Bio 26

      Pages: 409-418

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Enhanced biological activity of polymeric osteopontin2007

    • Author(s)
      Higashikawa, F., et. al.
    • Journal Title

      FEBS letter 581

      Pages: 2697-2701

    • NAID

      120000875265

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The integrin α5β1 regulates chondrocyte hypertrophic differentiation induced by GTP-bound transglutaminase 22007

    • Author(s)
      Tanaka, K
    • Journal Title

      Matrix Biology 26

      Pages: 409-418

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced biological activity of polymeric osteopontin2007

    • Author(s)
      Higashikawa, F
    • Journal Title

      FEBS Letters 581

      Pages: 2697-2701

    • NAID

      120000875265

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The integrin α5β1 regulates chondrocyte hypertrophic differentiation induced by GTP-bound transglutaminase 2

    • Author(s)
      Tanaka, K
    • Journal Title

      Matrix Biology (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Presentation] トランスグルタミナーゼ2はオステオポンチンを重合し好中球の遊走を惹起する2007

    • Author(s)
      横崎恭之
    • Organizer
      日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-12
    • Related Report
      2007 Annual Research Report
  • [Presentation] Polymeric Osteopontin is a Potent Chemoattractant for Neutrophils Mediated by Integrins.2007

    • Author(s)
      Yokosaki Y., et. al.
    • Organizer
      Gordon conference, Fibronectin, Integrins & Related molecules
    • Place of Presentation
      Lucca, Italy
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Polymerization of osteopontin enhances its biological activity.2007

    • Author(s)
      Yokosaki Y., et. al.
    • Organizer
      Gordon conference, Small integrin Binding-Proteins,
    • Place of Presentation
      Biddeford, ME, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] トランスグルタミナーゼ2はオステオポンチンを重合し好中球の遊走を惹起する2007

    • Author(s)
      横崎 恭之, 他
    • Organizer
      第30回日本分子生物学会・第80回日本生化学会合同年会(ワークショップ)
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Polymeric osteopontin is a potent chemoattractant for neutrophils mediated by Integrins2007

    • Author(s)
      Yokosaki, Y., et. al.
    • Organizer
      Gordon conference, Fibronectin, Integrins & Related molecules
    • Place of Presentation
      Lucca, Italy
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Polymerization of osteopontin enhances its biological activity2007

    • Author(s)
      Yokosaki, Y., et. al.
    • Organizer
      Gordon conference, Small integrin Binding-Proteins
    • Place of Presentation
      Biddeford, ME. USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Transglutaminase 2 induces neutrophil migration by polymerizing osteopontin2007

    • Author(s)
      Yokosaki, Y., et. al.
    • Organizer
      Molecular Biology Society of Japan (Work shop)
    • Place of Presentation
      Yokohama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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