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Downregulation of cPLA2 suppress diabetic nephropathy in diabetic mouse models

Research Project

Project/Area Number 17K09835
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionKumamoto University

Principal Investigator

Matsumura Takeshi  熊本大学, 大学院生命科学研究部(医), 准教授 (20398192)

Co-Investigator(Kenkyū-buntansha) 瀬ノ口 隆文  熊本大学, 大学院生命科学研究部(医), 助教 (00530320)
石井 規夫  熊本大学, 病院, 特任助教 (10599111)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords糖尿病性腎症 / 炎症 / マクロファージ / cPLA2 / 糖尿病 / 生体分子 / 糖尿病腎症
Outline of Final Research Achievements

It is a important theme that the prevention of diabetic nephropathy in Japan. Protein kinase C and subsequent cPLA2 is involved in the progression of diabetic nephropathy. However, it is unclear that the effect of cPLA2 inhibition on the progression of diabetic nephropathy. We revealed that the lack of cPLA2 suppressed the progression of diabetic nephropathy using cPLA2-deficient diabetic mice. The result suggests that the inhibition of cPLA2 is useful for the management of diabetic nephropathy.

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症は、慢性的な髙血糖により引き起こされる糖尿病特有の合併症であり、透析導入の原因として、我が国では1位を占める疾患である。しかし、現時点では血糖コントロール以外での腎症治療として有効な薬物はほとんどなく、早急な対策が必要な疾患である。我々はcPLA2欠損マウスを用いた検討で糖尿病性腎症の進展阻止を引き起こせる新たなターゲット分子としてcPLA2の可能性を見出した。本研究の成果から、毒性の少ないcPLA2阻害薬開発を行うことで、慢性腎不全に悩む多くの糖尿病患者の福音となる可能性が提示された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (32 results)

All 2020 2019 2018 2017

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 11 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 9 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Inhibition of inflammation-mediated DPP-4 expression by linagliptin increases M2 macrophages in atherosclerotic lesions2020

    • Author(s)
      Nishida Shuhei、Matsumura Takeshi、Senokuchi Takafumi、Murakami-Nishida Saiko、Ishii Norio、Morita Yutaro、Yagi Yoshitaka、Motoshima Hiroyuki、Kondo Tatsuya、Araki Eiichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 524 Issue: 1 Pages: 8-15

    • DOI

      10.1016/j.bbrc.2020.01.027

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyperemesis gravidarum followed by refeeding syndrome causes electrolyte abnormalities induced rhabdomyolysis and diabetes insipidus2019

    • Author(s)
      Kondo Tatsuya、Nakamura Miwa、Kawashima Junji、Matsumura Takeshi、Ohba Takashi、Yamaguchi Munekage、Katabuchi Hidetaka、Araki Eiichi
    • Journal Title

      Endocrine Journal

      Volume: 66 Issue: 3 Pages: 253-258

    • DOI

      10.1507/endocrj.EJ18-0496

    • NAID

      130007626248

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mineralocorticoid Receptor May Regulate Glucose Homeostasis through the Induction of Interleukin-6 and Glucagon-Like peptide-1 in Pancreatic Islets2019

    • Author(s)
      Goto Rieko、Kondo Tatsuya、Ono Kaoru、Kitano Sayaka、Miyakawa Nobukazu、Watanabe Takuro、Sakaguchi Masaji、Sato Miki、Igata Motoyuki、Kawashima Junji、Motoshima Hiroyuki、Matsumura Takeshi、Shimoda Seiya、Araki Eiichi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 8 Issue: 5 Pages: 674-674

    • DOI

      10.3390/jcm8050674

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pioglitazone suppresses macrophage proliferation in apolipoprotein-E deficient mice by activating PPARγ2019

    • Author(s)
      Murakami-Nishida Saiko、Matsumura Takeshi、Senokuchi Takafumi、Ishii Norio、Kinoshita Hiroyuki、Yamada Sarie、Morita Yutaro、Nishida Shuhei、Motoshima Hiroyuki、Kondo Tatsuya、Komohara Yoshihiro、Araki Eiichi
    • Journal Title

      Atherosclerosis

      Volume: 286 Pages: 30-39

    • DOI

      10.1016/j.atherosclerosis.2019.04.229

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential predictive factors for cardiovascular events in patients with or without cancer history.2019

    • Author(s)
      Sueta D, Tabata N, Ikeda S, Saito Y, Ozaki K, Sakata K, Matsumura T, Yamamoto-Ibusuki M, Murakami Y, Jodai T, Fukushima S, Yoshida N, Kamba T, Araki E, Iwase H, Fujii K, Ihn H, Kobayashi Y, Minamino T, Yamagishi M, Maemura K, Baba H, Matsui K, Tsujita K.
    • Journal Title

      Medicine (Baltimore).

      Volume: 98 Issue: 44 Pages: e17602-e17602

    • DOI

      10.1097/md.0000000000017602

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of hepatic HSP72 on insulin signaling2019

    • Author(s)
      Kitano Sayaka、Kondo Tatsuya、Matsuyama Rina、Ono Kaoru、Goto Rieko、Takaki Yuki、Hanatani Satoko、Sakaguchi Masaji、Igata Motoyuki、Kawashima Junji、Motoshima Hiroyuki、Matsumura Takeshi、Kai Hirofumi、Araki Eiichi
    • Journal Title

      American Journal of Physiology-Endocrinology and Metabolism

      Volume: 316 Issue: 2 Pages: E305-E318

    • DOI

      10.1152/ajpendo.00215.2018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of local macrophage growth ameliorates focal inflammation and suppresses atherosclerosis.2018

    • Author(s)
      Yamada S, Senokuchi T, Matsumura T, Morita Y, Ishii N, Fukuda K, Murakami S, Nishida S, Kawasaki S, Motoshima H, Furukawa N, Komohara Y, Fujiwara Y, Koga T, Yamagata K, Takeya M, Araki E
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 印刷中 Issue: 5 Pages: 994-1006

    • DOI

      10.1161/atvbaha.117.310320

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impacts of the 2016 Kumamoto Earthquake on glycemic control in patients with diabetes2018

    • Author(s)
      Kondo Tatsuya、Miyakawa Nobukazu、Motoshima Hiroyuki、Hanatani Satoko、Ishii Norio、Igata Motoyuki、Yoshinaga Kayo、Kukidome Daisuke、Senokuchi Takafumi、Kawashima Junji、Furukawa Noboru、Matsumura Takeshi、Araki Eiichi
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 10 Issue: 2 Pages: 521-530

    • DOI

      10.1111/jdi.12891

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The clinical course and pathophysiological investigation of adolescent gestational diabetes insipidus: a case report2018

    • Author(s)
      Kondo Tatsuya、Nakamura Miwa、Kitano Sayaka、Kawashima Junji、Matsumura Takeshi、Ohba Takashi、Yamaguchi Munekage、Katabuchi Hidetaka、Araki Eiichi
    • Journal Title

      BMC Endocrine Disorders

      Volume: 18 Issue: 1 Pages: 4-4

    • DOI

      10.1186/s12902-018-0234-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low glucose induces mitochondrial reactive oxygen species via fatty acid oxidation in bovine aortic endothelial cells.2017

    • Author(s)
      Kajihara N, Kukidome D, Sada K, Motoshima H, Furukawa N, Matsumura T, Nishikawa T, Araki E.
    • Journal Title

      J Diabetes Investig.

      Volume: 印刷中 Issue: 6 Pages: 750-761

    • DOI

      10.1111/jdi.12678

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] otential of Monocyte Count for the Assessment of Cardiovascular Disease.2017

    • Author(s)
      Matsumura T, Yamamoto E, Tsujita K, Araki E
    • Journal Title

      Cardiovascular Pharmacology

      Volume: 6 Issue: 05 Pages: 217-217

    • DOI

      10.4172/2329-6607.1000217

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ペマフィブラートに適した病態: どのような患者が適しているのか2017

    • Author(s)
      松村剛, 荒木栄一
    • Journal Title

      Progress in Medicine

      Volume: 37(9) Pages: 1047-1050

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 成因と治療 3)マクロファージ2017

    • Author(s)
      松村剛, 荒木栄一
    • Journal Title

      糖尿病

      Volume: 60(7) Pages: 481-484

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 2型糖尿病におけるHDL亜分画とインスリン抵抗性との関連2017

    • Author(s)
      松村 剛, 松嶋和美, 杉内博幸, 荒木栄一
    • Journal Title

      The Lipid

      Volume: 28(1) Pages: 92-97

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Effects of linagliptin on macrophages and on progression of atherosclerosis in high fat-fed apoE-deficient mice2019

    • Author(s)
      Nishida S, Matsumura T, Senokuchi T, Ishii N, Murakami-Nishida S, Yamada S, Morita Y, Wada T, Motoshima H, Kondo T, Araki E
    • Organizer
      The 11th Scientific Meeting of the Asian Association for the Study of Diabetes
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Hepatic Role of Heat Shock Protein 72 in the Pathogenesis of Type 2 Diabetes2019

    • Author(s)
      Kondo T, Kitano S, Miyakawa N, Watanabe T, Goto R, Ono K, Igata M, Kawashima J, Motoshima H, Matsumura T, Araki E
    • Organizer
      The 79th ADA Scientific Meetng
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pioglitazone Suppresses Macrophage Proliferation in Apolipoprotein-e Deficient Mice by Activating PPARγ2019

    • Author(s)
      Murakami-Nishida S, Matsumura T, Nishida S, Senokuchi T, Ishi N, Yamada S, Morita Y, Wada T, Motoshima H, Kondo T, Araki E
    • Organizer
      The 79th ADA Scientific Meetng
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Linagliptin induces M2 macrophage polarization and suppresses progression of atherosclerosis in high fat-fed apoE-deficient mice2019

    • Author(s)
      Nishida S, Matsumura T, Senokuchi T, Ishii N, Murakami-Nishida S, Yamada S, Morita Y, Wada T, Motoshima H, Kondo T, Araki E
    • Organizer
      The 79th ADA Scientific Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pioglitazone suppresses macrophage proliferation in apolipoprotein-E deficient mice by activating PPARγ2019

    • Author(s)
      Matsumura T, Murakami-Nishida S, Nishida S, Senokuchi T, Ishii N, Morita Y, Wada T, Motoshima H, Kondo T, Arak E
    • Organizer
      55th Annual Meetng of the European Association of the Study of Diabetes
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The organ cross talk in the regulation of glucose homeostasis through heat shock protein 72 expression2019

    • Author(s)
      Kondo T, Kitano S, Miyakawa N, Watanabe T, Goto R, Igata M, Kawashima J, Motoshima H, Matsumura T, Araki E
    • Organizer
      55th Annual Meetng of the European Association of the Study of Diabetes
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of DPP-4 suppresses atherosclerotic lesion formation through the regulation of M2 macrophage polarization2019

    • Author(s)
      Yagi Y, Matsumura T, Nishida S, Senokuchi T, Ishii N, Murakami-Nishida S, Morita Y, Wada T, Motoshima H, Kondo T, Araki E
    • Organizer
      IDF Congress 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of Tissue Macrophages Proliferation in Insulin Resistance in the Liver and Adipose tissue2019

    • Author(s)
      Wada T, Senokuchi T, Yamada S, Morita Y, Furusho T, Motoshima H, Ishi N, Matsumura T, Araki E
    • Organizer
      IDF Congress 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糖尿病患者における肝細胞癌発生の実態調査2019

    • Author(s)
      松村剛,瀬ノ口隆文,建石良介,窪田直人,小池和彦,荒木栄一
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ピオグリタゾンによるマクロファージ増殖抑制効果を介した糖尿病大血管合併症進展抑制効果2019

    • Author(s)
      松村剛,西田彩子,瀬ノ口隆文,石井規夫,山田沙梨恵,守田雄太郎,西田周平,和田敏明, 佐藤美希,本島寛之,近藤龍也,荒木栄一
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Empagliflozin suppresses atherosclerotic lesion formation in apolipoprotein E deficient mice by inhibiting macrophage activation.2018

    • Author(s)
      Takeshi Matsumura
    • Organizer
      54th EASD Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 基礎研究から読み取る糖尿病大血管合併症発症機序とその臨床的意義2018

    • Author(s)
      松村 剛
    • Organizer
      第56回日本糖尿病学会 九州地方会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 糖尿病患者における肝細胞癌発生の実態調査2018

    • Author(s)
      松村 剛,瀬ノ口隆文,建石良介,小池和彦,荒木栄一
    • Organizer
      第68回日本体質医学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 動脈硬化と体質2017

    • Author(s)
      松村 剛, 瀬ノ口隆文, 荒木栄一
    • Organizer
      第67回日本体質医学会年次学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, suppresses the progression of atherosclerosis in diabetic apoE-deficient mice.2017

    • Author(s)
      1.Matsumura T, Murakami S, Senokuchi T, Ishii N, Fukuda K, Nishida S, Araki E
    • Organizer
      第81回日本循環器学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 熊本地震後における治療中断に関する実態調査-治療中断の背景と糖尿病患者に与える影響-2017

    • Author(s)
      松村 剛, 上田聖子, 藤本有紀, 深田和子, 吉富咲子, 坂口春花, 早田有希, 山田沙梨恵, 荒木栄一
    • Organizer
      第60回日本糖尿病学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 2型糖尿病患者における網膜症進展の予測因子に関する解析2017

    • Author(s)
      松村 剛, 本島寛之, 近藤龍也, 瀬ノ口隆文, 河島淳司, 久木留大介, 井形元維, 吉永佳代, 荒木栄一
    • Organizer
      第55回日本糖尿病学会九州地方会
    • Related Report
      2017 Research-status Report
  • [Book] 日本臨床75巻 増刊号4 動脈・静脈の疾患(上) 最新の診断・治療動向.2017

    • Author(s)
      松村 剛, 荒木栄一
    • Total Pages
      554
    • Publisher
      日本臨牀社
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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