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Molecular pharmacological analysis of anti-inflammatory effects of PAI-1 inhibitor

Research Project

Project/Area Number 25860185
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionKyoto University (2014)
Tohoku University (2013)

Principal Investigator

ATSUHIKO Ichimura  京都大学, 健康長寿社会の総合医療開発ユニット, 特定助教 (10609209)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords分子薬理学 / 創薬 / 炎症 / 薬理学 / 糖尿病 / 肥満 / 代謝
Outline of Final Research Achievements

This research was conducted with the aim to elucidate the molecular pharmacological mechanism of anti-inflammatory effect of PAI-1 inhibitors. The suitable pathological model of inflammation to evaluate efficacy of PAI-1 inhibitors was searched. As a result, we have successfully found anti-inflammatory effect of PAI-1 inhibitors on high fat diet (HFD)-induced obesity model. PAI-1 inhibitors attenuated HFD-induced impaired systemic glucose and energy metabolism. Further analyses of molecular mechanisms of the efficacy of PAI-1 inhibitors demonstrated that PAI-1 inhibitors suppressed accumulation of fat in adipocyte accompanying with the inhibition of infiltration of inflammatory macrophages into adipose tissue and the liver. These results suggest the possibility of PAI-1 inhibitors as novel therapeutic agent of metabolic disorders.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2015 2014 2013

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results)

  • [Journal Article] Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer.2015

    • Author(s)
      Mashiko S, Kitatani K, Toyoshima M, Ichimura A, Dan T, Usui T, Ishibashi M, Shigeta S, Nagase S, Miyata T, Yaegashi N
    • Journal Title

      Cancer Biology & Therapy

      Volume: 16 Issue: 2 Pages: 253-260

    • DOI

      10.1080/15384047.2014.1001271

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A Novel Antidiabetic Therapy: free Fatty Acids Receptors as Potential Druggable Targets.2015

    • Author(s)
      Sekiguchi H, Kasubuchi M, Hasegawa S, Pelisch N, Kimura I, Ichimura A.
    • Journal Title

      Curr Diabetes Rev.

      Volume: -

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Plasminogen activator inhibitor-1 (PAI-1) molecule: new physiological roles and clinical applications.2014

    • Author(s)
      Dan T, Ichimura A, Pelisch N, Miyata K, Akahori K, Miyata T.
    • Journal Title

      Rinsho Ketsueki.

      Volume: 55 Pages: 396-404

    • NAID

      130004920665

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Therapeutic role and ligands of medium- to long-chain Fatty Acid receptors.2014

    • Author(s)
      Hara T, Ichimura A, Hirasawa A.
    • Journal Title

      Front Endocrinol

      Volume: 5 Pages: 83-83

    • DOI

      10.3389/fendo.2014.00083

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of free fatty acid receptors in the regulation of energy metabolism2014

    • Author(s)
      T. Hara, D. Kashihara, A. Ichimura, I. Kimura, G. Tsujimoto, and A. Hirasawa.
    • Journal Title

      Biochem Biophys Acta

      Volume: 1841 Issue: 9 Pages: 1292-1300

    • DOI

      10.1016/j.bbalip.2014.06.002

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Energy Homeostasis via GPR120.2014

    • Author(s)
      Ichimura A, Hara T, Hirasawa A.
    • Journal Title

      Front Endocrinol

      Volume: 11 Pages: 111-111

    • DOI

      10.3389/fendo.2014.00111

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Free fatty acids receptors as therapeutic target for treatment of diabetes.2014

    • Author(s)
      A. Ichimura, S. Hasegawa, M. Kasubuchi, and I. Kimura*
    • Journal Title

      Front Pharmacol.

      Volume: 5 Pages: 236-236

    • DOI

      10.3389/fphar.2014.00236

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The PAI-1 antagonist TM5441 attenuates L-NAME-induced hypertension and vascular senescence2013

    • Author(s)
      Boe A, Eren M, Murphy S, Kamide1 C, Ichimura A, Terry D, McAnally D, Smith LH, Miyata T, Vaughan DE
    • Journal Title

      Circulation

      Volume: 128 Issue: 21 Pages: 2318-2324

    • DOI

      10.1161/circulationaha.113.003192

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Free Fatty Acid Receptors and Their Role in Regulation of Energy Metabolism.2013

    • Author(s)
      Hara Takafumi, et al.
    • Journal Title

      Reviews of Physiology, Biochemistry and Pharmacology

      Volume: - Pages: 77-116

    • DOI

      10.1007/112_2013_13

    • ISBN
      9783319009957, 9783319009964
    • Related Report
      2013 Research-status Report
    • Peer Reviewed

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Published: 2014-07-25   Modified: 2019-07-29  

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