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A new strategy of the regulation of metabolic syndrome and cardiovascular diseases by the pharmacological targeting of cellular mechanical stress reactions.

Research Project

Project/Area Number 22616007
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Mechanobiology
Research InstitutionIwate Medical University

Principal Investigator

TANABE Yoshiyuki  岩手医科大学, 薬学部, 准教授 (10275109)

Co-Investigator(Kenkyū-buntansha) SAITO Maki  岩手医科大学, 薬学部, 助教 (40365185)
鎌滝 章央  岩手医科大学, 医学部, 助教 (60360004)
Co-Investigator(Renkei-kenkyūsha) KAMATAKI Akihisa  岩手医科大学, 医学部, 助教 (60360004)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsメカニカルストレス / メタボリックシンドローム / 脂肪細胞 / マクロファージ / PPAR-γ / サイトカイン / 肺高血圧 / ホスホリパーゼA2 / 脂肪組織 / シクロオキシゲナーゼ / sPLA2 / アディポサイトカイン / 肺高血圧症 / アポトーシス
Research Abstract

The effects of abdominal vibration were examined using obese mice with high-fat diet. Daily exposure of the 30-minutes-vibration induced downregulation of adipogenic factors and upregulation of anti-adipogenic factor, which consisted with decreasing adipose tissue triglyceride, some adipokines, and plasma free fatty acids. Furthermore, augmented expressions of several genes characteristic of anti-inflammatory M2 macrophages (Mφ) were detected. The effects of selective sPLA2 inhibitor (indoxam) on the pathogenicity of MCT-induced fatal pulmonary hypertensive rats (MCT-PHR) were also examined. Indoxam abolished the enhanced contractilities of the pulmonary arteries of MCT-PHR, which arteries show augmented expression of sPLA2-X isoform. In addition, administration of indoxam attenuated some inflammatory signs such as expression of proinflammatory cytokines and apoptosis in the lung, leading to a significant improvement of survival ratio in MCT-PHR.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (27 results)

All 2013 2012 2011 2010 Other

All Journal Article (8 results) (of which Peer Reviewed: 6 results) Presentation (19 results)

  • [Journal Article] Involvement of secretory phospholipase A2 in the rhythmic contraction of pulmonary arteries produced by stretching in monocrotaline-induced pulmonary arterial hypertensive rats and possible implication for the pathogenicity.2013

    • Author(s)
      Saito M, Tanabe Y, Kamataki A, Sawai T, Nakayama K
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 121 (suppl.)

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Mechanosensitivity of pancreatic β-cells, adipocytes, and skeletal muscle cells: the therapeutic targets of metabolic syndrome.2012

    • Author(s)
      Nakayama K, Tanabe Y, Obara K, Ishikawa T
    • Journal Title

      Mechanosensitivity in Cells and Tissues

      Volume: 6 Pages: 379-404

    • DOI

      10.1007/978-94-007-5073-9_14

    • ISBN
      9789400750722, 9789400750739
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of Secretory Phospholipase A<SUB>2</SUB> in Rhythmic Contraction of Pulmonary Arteries of Rats With Monocrotaline-Induced Pulmonary Arterial Hypertension2012

    • Author(s)
      Tanabe Y, Saito-Tanji M, Morikawa Y, Kamataki A, Sawai T, Nakayama K
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 119 Issue: 3 Pages: 271-281

    • DOI

      10.1254/jphs.12024FP

    • NAID

      10030987037

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Indoxam, a phospholipase A2 inhibitor, prolongs survival period without lowering pulmonary arterial pressure in rats with monocrotaline-induced pulmonary hypertension2012

    • Author(s)
      Saito M, Tanabe Y, Kamataki A, Sawai T, Kanno M, Hirose M, Nakayama K
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 118(suppl1) Pages: 214-214

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Rho and Rho-kinase activity in adipocytes contributes to a vicious cycle in obesity that may involve mechanical stretch2011

    • Author(s)
      Hara Y, et al
    • Journal Title

      Sci Signal

      Volume: 4 Issue: 157

    • DOI

      10.1126/scisignal.2001227

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Untransformed Prostaglandin H2 Production and Stretch-Induced Contraction of Rabbit Pulmonary Arteries by Indoxam, a Selective Secretory Phospholipase A2 Inhibitor2011

    • Author(s)
      Tanabe Y, Saito M, Morikawa Y, Kamataki T, Sawai T, Hirose M, Nakayama K.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 115 Issue: 4 Pages: 525-531

    • DOI

      10.1254/jphs.10247SC

    • NAID

      10029893573

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of untransformed PGH_2-production and stretch-induced contraction of rabbit pulmonary arteries by indoxam, a selective sPLA_2 inhibitor.2011

    • Author(s)
      Tanabe Y, Saito M, Morikawa Y, Kamataki A, Sawai T, Hirose M, Nakayama K.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 115(印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rho and rho-kinase activity in adipocytes contributes to a vicious cycle in obesity that may involve mechanical stretch.2011

    • Author(s)
      Hara Y, Wakino S, Tanabe Y, Saito M, Tokuyama H, Washida N, Tatematsu S, Yoshioka K, Homma K, Hasegawa K, Minakuchi H, Fujimura K, Hosoya K, Hayashi K, Nakayama K, Itoh H.
    • Journal Title

      Science Signaling

      Volume: 4

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 分泌型ホスホリパーゼA2の力学刺激による肺動脈の収縮性亢進機構への関与と実験的肺高血圧症における病態形成との関連2013

    • Author(s)
      丹治(斉藤)麻希、田辺由幸、鎌滝章央、澤井高志、中山貢一
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡市、福岡国際会議場
    • Year and Date
      2013-03-22
    • Related Report
      2012 Final Research Report
  • [Presentation] 腹部振動刺激が肥満マウスの脂肪組織および代謝内分泌機能に及ぼす効果の解析2012

    • Author(s)
      田辺由幸、丹治(斉藤)麻希、鎌滝章央、澤井高志、中山貢一
    • Organizer
      第63回 日本薬理学会北部会
    • Place of Presentation
      新潟市、朱鷺メッセ
    • Year and Date
      2012-09-14
    • Related Report
      2012 Final Research Report
  • [Presentation] バイオメカニカルストレス反応と細胞制御:肺高血圧時肺動脈の収縮緊張性異常への関与ならびに脂肪細胞・組織における細胞分化・代謝機能制御の試み(ポスターおよび口頭)2012

    • Author(s)
      田辺由幸、丹治(斉藤)麻希、鎌滝章央、澤井高志、中山貢一
    • Organizer
      第6回 先端医療薬学研究センター講演会薬と医・歯の連携へ ~基礎から応用まで~
    • Place of Presentation
      岩手県矢巾町
    • Year and Date
      2012-03-16
    • Related Report
      2012 Final Research Report
  • [Presentation] 分泌型ホスホリパーゼA2阻害薬インドキサムは肺動脈圧の低下無しにモノクロタリン誘発肺高血圧症ラットの生存期間を延長する2012

    • Author(s)
      斉藤麻希、田邉由幸、鎌滝章央、澤井高志、菅野美紅、中山貢一.
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都
    • Year and Date
      2012-03-15
    • Related Report
      2012 Final Research Report
  • [Presentation] 分泌型ホスホリパーゼA2阻害薬インドキサムは肺動脈圧の低下無しにモノクロタリン誘発肺高血圧症ラットの生存期間を延長する2012

    • Author(s)
      斉藤麻希、田邉由幸、鎌滝章央、澤井高志、菅野美紅、弘瀬雅教、中山貢一
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2012-03-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] バイオメカニカルストレス反応と細胞制御:肺高血圧時肺動脈の収縮緊張性異常への関与ならびに脂肪細胞・組織における細胞分化・代謝機能制御の試み2012

    • Author(s)
      田辺由幸、斉藤麻希、鎌滝章央、澤井高志、中山貢一
    • Organizer
      第6回先端医療薬学研究センター講演会薬と医・歯の連携へ~基礎から応用まで~
    • Place of Presentation
      岩手医科大学矢巾キャンパス
    • Year and Date
      2012-03-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] バイオメカニカルストレスによる脂肪細胞・組織での細胞分化・代謝機能制御の試み2012

    • Author(s)
      田辺由幸、丹治(斉藤)麻希、鎌滝章央、澤井高志、中山貢一
    • Organizer
      第13回 Pharmaco-Hematologyシンポジウム「血液からの創薬を考える」
    • Place of Presentation
      東京 日本薬学会長井記念ホール
    • Related Report
      2012 Final Research Report
  • [Presentation] 力学刺激による脂肪細胞機能の制御機構Mechanisms for regulation of adipocyte functions by mechanical stimulation.(シンポジウム メタボリックシンドローム2011-次なるdecadeにむけて)2011

    • Author(s)
      田邉由幸, 斎藤麻希, 鎌滝章央, 澤井高志, 弘瀬雅教, 中山貢一
    • Organizer
      薬学会131年会(静岡)
    • Place of Presentation
      (東日本大震災のため誌上開催に変更)
    • Year and Date
      2011-03-31
    • Related Report
      2010 Annual Research Report
  • [Presentation] モノクロタリン肺高血圧ラットに対するsPLA2阻害薬インドキサムの予後改善効果Indoxam, a sPLA2 inhibitor, shows life-prolonging effect on monocrotaline-induced pulmonary arterial hypertension in rats2011

    • Author(s)
      斎藤麻希、田邉由幸, 鎌滝章央, 澤井高志, 弘瀬雅教, 中山貢一
    • Organizer
      薬学会131年会(静岡)
    • Place of Presentation
      (東日本大震災のため誌上開催に変更)
    • Year and Date
      2011-03-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] 分泌型ホスホリパーゼA_2阻害によるモノクロタリン肺高血圧ラット生存率の改善Survival advantage of secretory phospholipase A_2 inhibition in rats with monocrotalineinduced pulmonary arterial hypertension2011

    • Author(s)
      斎藤麻希、田邉由幸、鎌滝章央、弘瀬雅教、澤井高志、中山貢一
    • Organizer
      第84回 日本薬理学会年会Journal of Pharmacological Sciences, 115(suppl.1), 2011
    • Place of Presentation
      (東日本大震災のため誌上開催に変更)
    • Year and Date
      2011-03-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 分泌型ホスホリパーゼA2阻害によるモノクロタリン肺高血圧ラット生存率の改善2011

    • Author(s)
      斉藤麻希、田邉由幸、鎌滝章央、澤井高志、中山貢一
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      東日本大震災のため誌上開催
    • Related Report
      2012 Final Research Report
  • [Presentation] 力学刺激による脂肪細胞機能の制御機構2011

    • Author(s)
      田邉由幸、斉藤麻希、鎌滝章央、澤井高志、中山貢一
    • Organizer
      日本薬学会131年会一般シンポジウム・メタボリックシンドロームの分子メカニズム2011 -次なるDecadeに向けて-
    • Place of Presentation
      東日本大震災のため、誌上開催
    • Related Report
      2012 Final Research Report
  • [Presentation] モノクロタリン肺高血圧ラットに対するsPLA2 阻害薬インドキサムの予後改善効果2011

    • Author(s)
      斉藤麻希、田邉由幸、鎌滝章央、澤井高志、中山貢一.
    • Organizer
      日本薬学会131年会
    • Place of Presentation
      東日本大震災のため誌上開催
    • Related Report
      2012 Final Research Report
  • [Presentation] Involvement of secretory phospholipase A2 in stretch-induced aberrant contraction in pulmonary arteries isolated from pulmonary hypertensiverats2010

    • Author(s)
      Saito M, Tanabe Y, Kamataki A, Sawai T, Nakayama K.
    • Organizer
      the 16^<th> World Congress of Basic and Clinical Pharmacology
    • Place of Presentation
      Copenhagen, Denmark
    • Year and Date
      2010-06-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 分泌型ホスホリパーゼ A2 阻害薬のモノクロタリン誘発肺高血圧症ラットに対する延命効果2010

    • Author(s)
      斉藤麻希、田邉由幸、鎌滝章央、澤 井 高 志 、 中 山 貢 一
    • Organizer
      第11回Pharmaco-Hematology
    • Place of Presentation
      シンポジウム(東京)
    • Year and Date
      2010-06-19
    • Related Report
      2012 Final Research Report
  • [Presentation] 分泌型ホスホリパーゼA_2阻害薬のモノクロタリン誘発肺高血圧症ラットに対する延命効果2010

    • Author(s)
      斎藤麻希, 田邉由幸、鎌滝章央, 澤井高志, 中山貢一
    • Organizer
      第11回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      日本薬学会長井記念ホール(渋谷・東京)
    • Year and Date
      2010-06-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] バイオメカニカルストレスによる脂肪細胞・組織での細胞分化・代謝機能制御の試み

    • Author(s)
      田辺由幸、丹治(斉藤)麻希、鎌滝章央、澤井高志、中山貢一
    • Organizer
      第13回 Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      東京、日本薬学会長井記念ホール
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腹部振動刺激が肥満マウスの脂肪組織および代謝内分泌機能に及ぼす効果の解析

    • Author(s)
      田辺由幸、丹治(斉藤)麻希、鎌滝章央、澤井高志、中山貢一
    • Organizer
      第63回 日本薬理学会北部会
    • Place of Presentation
      新潟市、朱鷺メッセコンベンションセンター
    • Related Report
      2012 Annual Research Report
  • [Presentation] 分泌型ホスホリパーゼA2の力学刺激による肺動脈の収縮性亢進機構への関与と実験的肺高血圧症における病態形成との関連

    • Author(s)
      丹治(斉藤)麻希、田辺由幸、鎌滝章央、澤井高志、中山貢一
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡市、福岡国際会議場
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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