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Elucidation of mechanisms of action of the growth factor midkine which is involved in inter-organ crosstalk regulating inflammation and blood pressure

Research Project

Project/Area Number 23390078
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

KADOMATSU Kenji  名古屋大学, 医学(系)研究科(研究院), 教授 (80204519)

Co-Investigator(Kenkyū-buntansha) TAKEI Yoshifumi  名古屋大学, 医学系研究科, 准教授 (70362233)
KISHIDA Satoshi  名古屋大学, 医学系研究科, 助教 (20402563)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2011: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Keywords成長因子 / ミッドカイン / 血圧 / 受容体 / 血管内皮
Research Abstract

The aim of this research is to elucidate midkine (MK) receptor and its downstream signaling by focusing on MK's function in endothelium and inter-organ crosstalk. We developed RNA aptamer and antibody, which strongly inhibited MK binding to the cell as well as tumorigenesis. We also found dynamic expression changes of many molecules including H1FX downstream of MK. Furthermore, we demonstrated that MK-deficient mice did not show hypertension in a model of endothelial injury using a NO synthase inhibitor. The underlying mechanism was that MK suppressed the production of EET which is a candidate EDHF. EDHF is a vasodilator. MK probably suppresses A2AR, which in turn suppresses the activity of CYP450and the production of EET.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (33 results)

All 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 1 results) Presentation (7 results) (of which Invited: 5 results) Book (2 results) Remarks (5 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] A new tumorsphere culture condition restores potentials of self-renewal and metastasis of primary neuroblastoma in a mouse neuroblastoma model2014

    • Author(s)
      Cao D, Kishida S, Huang P, Mu P, Tsubota S, Mizuno M, Kadomatsu K
    • Journal Title

      PLoS One

      Volume: 9(1)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Midkine : an emerging target of drug development for treatment of multiple diseases2014

    • Author(s)
      Muramatsu T, Kadomatsu K
    • Journal Title

      Br J Pharmacol

      Volume: 171(4) Issue: 4 Pages: 811-813

    • DOI

      10.1111/bph.12571

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic potential of midkine in cardiovascular disease2014

    • Author(s)
      Kadomatsu K, Bencsik P, Görbe A, Csonka C, Sakamoto K, Kishida S, Ferdinandy P
    • Journal Title

      Br J Pharmacol

      Volume: 171(4) Issue: 4 Pages: 936-944

    • DOI

      10.1111/bph.12537

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of midkine in neuroblastoma tumourigenesis2014

    • Author(s)
      Kishida S, Kadomatsu K
    • Journal Title

      Br J Pharmacol

      Volume: 171(4) Issue: 4 Pages: 896-904

    • DOI

      10.1111/bph.12442

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new tumorsphere culture condition restores potentials of self-renewal and metastasis of primary neuroblastoma in a mouse neuroblastoma model.2014

    • Author(s)
      Cao D, Kishida S, Huang P, Mu P, Tsubota S, Mizuno M, Kadomatsu K.
    • Journal Title

      PLoS One.

      Volume: 9

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Midkine overcomes neurite outgrowth inhibition of chondroitin sulfate proteoglycan without glial activation and promotes functional recovery after spinal cord injury.2013

    • Author(s)
      Muramoto A, Imagama S, Natori T, Wakao N, Ando K, Tauchi R, Hirano K, Shinjo R, Matsumoto T, Ishiguro N, Kadomatsu K.
    • Journal Title

      Neurosci Lett.

      Volume: 550 Pages: 150-155

    • DOI

      10.1016/j.neulet.2013.06.025

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The heparin-binding growth factor midkine : the biological activities and candidate receptors2013

    • Author(s)
      Kadomatsu K, Kishida S, Tsubota S
    • Journal Title

      J Biochem

      Volume: 153(6) Issue: 6 Pages: 511-521

    • DOI

      10.1093/jb/mvt035

    • NAID

      40019655639

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Midkine promotes neuroblastoma through Notch2 signaling2013

    • Author(s)
      Kishida S, Mu P, Miyakawa S, Fujiwara M, Abe T, Sakamoto K, Onishi A, Nakamura Y, Kadomatsu K
    • Journal Title

      Cancer Res

      Volume: 73(4) Issue: 4 Pages: 318-327

    • DOI

      10.1158/0008-5472.can-12-3070

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of growth factor midkine exacerbates necrotizing glomerular injuries in progressive glomerulonephritis2013

    • Author(s)
      Kojima H, Kosugi T, Sato W, Sato Y, Maeda K, Kato N, Kato K, Inaba S, Ishimoto T, Tsuboi N, Matsuo S, Maruyama S, Yuzawa Y, Kadomatsu K
    • Journal Title

      Am J Pathol

      Volume: 182(2) Issue: 2 Pages: 410-419

    • DOI

      10.1016/j.ajpath.2012.10.016

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of midkine in normal human skin, dermatitis and neoplasms: association with differentiation of keratinocytes.2013

    • Author(s)
      Monma F, Hozumi Y, Ikematsu S, Kawaguchi M, Kadomatsu K, Suzuki T.
    • Journal Title

      J Dermatol.

      Volume: 40 Issue: 12 Pages: 980-986

    • DOI

      10.1111/1346-8138.12333

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovering combinatorial interactions in survival data2013

    • Author(s)
      David duVerle, Ichiro Takeuchi, Yuko Murakami-Tonami, Kenji kadomatsu, Koji Tsuda
    • Journal Title

      Bio in formatics

      Volume: 23 Issue: 23 Pages: 3053-3059

    • DOI

      10.1093/bioinformatics/btt532

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Midkine in the pathology of cancer, neural disease, and inflammation2012

    • Author(s)
      Sakamoto K, Kadomatsu K
    • Journal Title

      Pathol Int

      Volume: 62(7) Issue: 7 Pages: 445-455

    • DOI

      10.1111/j.1440-1827.2012.02815.x

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Midkine inhibits inducible regulatory T cell differentiation by suppressing the development of tolerogenic dendritic cells2012

    • Author(s)
      SONOBE Yoshifumi
    • Journal Title

      Journal of Immunology

      Volume: 188(6) Issue: 6 Pages: 2602-2611

    • DOI

      10.4049/jimmunol.1102346

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts : a novel therapeutic approach for acute coronary syndrome2011

    • Author(s)
      Ishiguro H, Horiba M, Takenaka H, Sumida A, Opthof T, Ishiguro YS, Kadomatsu K, Murohara T, Kodama I
    • Journal Title

      Front Physiol

      Volume: 2 Pages: 27-27

    • DOI

      10.3389/fphys.2011.00027

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Neuronal Differentiation Factor NeuroD1 Downregulates the Neuronal Repellent Factor Slit2 Expression and Promotes Cell Motility and Tumor Formation of Neuroblastoma2011

    • Author(s)
      Peng Huang, Satoshi Kishida, Dongliang Cao, Yuko Murakami-Tonami, Ping Mu, Masato Nakaguro, Naoshi Koide, Ichiro Takeuchi, Akira Onishi, Kenji Kadomatsu
    • Journal Title

      Cancer Research

      Volume: 71 Issue: 8 Pages: 2938-48

    • DOI

      10.1158/0008-5472.can-10-3524

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin.2011

    • Author(s)
      Kato K
    • Journal Title

      Clin Exp Nephrol

      Volume: 15 Issue: 3 Pages: 346-54

    • DOI

      10.1007/s10157-011-0408-2

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Biomedical research at Nagoya University2014

    • Author(s)
      Kadomatsu, K.
    • Organizer
      International joint symposium Nagoya University, University of Adelaide, University of Freiburg
    • Place of Presentation
      Nagoya University, Nagoya
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 糖鎖と神経の融合研究へ ~硫酸化糖鎖と神経回路再編~2013

    • Author(s)
      門松健治
    • Organizer
      生化学会大会シンポジウム「脳神経回路の可塑性の生化学研究:分子メカニズムから疾患まで2013
    • Place of Presentation
      横浜国際会議場、横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Midkine : at the intersection of neurobiology and cancer2012

    • Author(s)
      Kadomatsu, K
    • Organizer
      Excellence in midkine research conference
    • Place of Presentation
      Istanbul, Turkey
    • Related Report
      2013 Final Research Report
  • [Presentation] A link between two sugar chains, keratan sulfate and chondroitin sulfate, in axonal regeneration/sprouting.2012

    • Author(s)
      Kadomatsu, K.
    • Organizer
      GCOE International Symposium.
    • Place of Presentation
      Hilton hotel, Nagoya
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 「神経糖鎖生物学」の目指すもの2012

    • Author(s)
      門松健治
    • Organizer
      3領域合同シンポジウム 夏の包括脳ワークショップ
    • Place of Presentation
      仙台国際センター、仙台市
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] サイトカイン, ケモカインとがん モーニングレクチャー2011

    • Author(s)
      門松健治
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場名古屋市
    • Year and Date
      2011-10-04
    • Related Report
      2013 Final Research Report
  • [Presentation] サイトカイン、ケモカインとがん2011

    • Author(s)
      門松健治
    • Organizer
      第70回日本癌学会総会 モーニングレクチャー
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Book] Midkine and chemoresistance in cancers. Midkine: From Embryogenesis to Pathogenesis and Therapy2012

    • Author(s)
      Takei Y, Kadomatsu K
    • Total Pages
      319
    • Publisher
      Springer
    • Related Report
      2013 Final Research Report
  • [Book] Vascular restenosis and midkine. Midkine and chemoresistance in cancers. Midkine: From Embryogenesis to Pathogenesis and Therapy2012

    • Author(s)
      Kadomatsu K
    • Total Pages
      319
    • Publisher
      Springer
    • Related Report
      2013 Final Research Report
  • [Remarks] 名古屋大学大学院医学系研究科分子生物学

    • URL

      http://www.med.nagoya-u.ac.jp/biochem/

    • Related Report
      2013 Final Research Report
  • [Remarks] 名古屋大学大学院医学系研究科分子生物学

    • URL

      http://www.med.nagoya-u.ac.jp/biochem/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 名古屋大学大学院医学系研究科分子生物学

    • URL

      http://www.med.nagoya-u.ac.jp/biochem/

    • Related Report
      2012 Annual Research Report
  • [Remarks] 名古屋大学大学院医学系研究科分子生物学

    • URL

      http://www.med.nagoya-u.ac.jp/biochem/

    • Related Report
      2011 Annual Research Report
  • [Remarks] 新学術研究領域 神経糖鎖生物学

    • URL

      http://shinkei-tosa.net/

    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] エポキシエイコサトリエン酸関連疾患の予防又は治療2012

    • Inventor(s)
      門松健治, 佐藤和一, 佐藤由香
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-06-29
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] ヒトミッドカインに対するモノクローナル抗体2012

    • Inventor(s)
      門松健治, 岸田聡, 小野健一郎, 八木香澄
    • Industrial Property Rights Holder
      名古屋大学, 株式会社医学生物学研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-07-30
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] ミッドカインに対するアプタマー及びその用途2012

    • Inventor(s)
      宮川伸, 藤原将寿, 中村義一, 門松健治,牟萍
    • Industrial Property Rights Holder
      名古屋大学, 株式会社リボミック
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-11-21
    • Related Report
      2013 Final Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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