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2010 Fiscal Year Final Research Report

Moleular Basis for HGF-mediated Self-defense System During sepsis

Research Project

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Project/Area Number 20590398
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionOsaka University

Principal Investigator

MIZUNO Shinya  Osaka University, 医学系研究科, 助教 (10219644)

Co-Investigator(Renkei-kenkyūsha) NAKAMURA Toshikazu  大阪大学, 先端科学イノベーションセンター, 特任教授 (00049397)
Project Period (FY) 2008 – 2010
KeywordsHGF / c-Met / 多臓器不全 / 敗血症 / 炎症性サイトカイン / マクロファージ
Research Abstract

We demonstrated that direct effects of HGF on macrophages during leads to inhibition of the NF-?b activation and subsequent transcription of pro-inflammatory cytokines. Furthermore, we found, using a mouse model of sepsis, that HGF-mediated up-regulation of hemeoxygenese-1 is required for HGF to inhibit the onset of septic acute renal failure, lung injury and hepatitis. Based on the present data, we conclude that enhancement of the HGF-hemeoxygenase-1 pathway in macrophages can be a reasonable strategy to improve the sepsis-related pathological conditions.

  • Research Products

    (29 results)

All 2011 2010 2009 2008 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (10 results) Book (2 results)

  • [Journal Article] Recombinant human HGF, but not rat HGF, elicits glomerular injury and albuminuria in normal rats via an immune complex-dependent mechanism.2011

    • Author(s)
      Mizuno S, Ikebuch F, Fukuta K, Kato T. Matsumoto K, Adachi K, Abe. Nakamura.
    • Journal Title

      Clin Exp Pharmacol Physiol 38

      Pages: 192-201

    • Peer Reviewed
  • [Journal Article] Preser.ations of nephrin and synaptopodin by HGF in podocytes for the attenuations of foot process injury and albuminuria in nephritic mice.2011

    • Author(s)
      Kato Y., Mizuno S, Nakamura T.
    • Journal Title

      Nephrology 16

      Pages: 310-318

    • Peer Reviewed
  • [Journal Article] Disco.ery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine.2010

    • Author(s)
      Nakamura T, Mizuno S.
    • Journal Title

      Proc. Japan Acad. Series-B 86

      Pages: 588-610

    • Peer Reviewed
  • [Journal Article] The decreases of nephrin and nuclear WT1 in podocytes may cause albuminuria during the experimental sepsis in mice.2010

    • Author(s)
      Kato T., Mizuno S, Kamimoto M.
    • Journal Title

      Biomed Res 1

      Pages: 363-369

    • Peer Reviewed
  • [Journal Article] Attenuation of ischemic myocardial injury and dysfunction by cardiac fibroblast-derived factor(s).2010

    • Author(s)
      Nakazato K, Naganuma W, Ogawa K, Yaoita H, Mizuno S, Nakamura T, Maruyama Y.
    • Journal Title

      Fukushima J Med Sci 56

      Pages: 1-16

    • Peer Reviewed
  • [Journal Article] Type 2a sodium-phosphate co-transporter serves as a histological predictor of renal dysfunction and tubular apical damage in the kidneys of septic mice.2009

    • Author(s)
      Kamimoto M, Mizuno S, Ohnishi H, Mizuno-Horikawa Y.
    • Journal Title

      Biomed Res 30

      Pages: 251-258

    • Peer Reviewed
  • [Journal Article] Systemic NK4 gene therapy inhibits tumor growth and metastasis of melanoma and lung carcinoma in syngeneic mouse tumor models.2009

    • Author(s)
      Kishi Y, Kuba K, Nakamura T, Wen J, Suzuki Y, Mizuno S, Nukiwa T, Matsumoto K, Nakamura T.
    • Journal Title

      Cancer Sci 100

      Pages: 1351-1358

    • Peer Reviewed
  • [Journal Article] Tryptophan 2,3-dioxygenase is a key modulator of physiological neugenesis and anxiety-related behavior in mice.2009

    • Author(s)
      Kanai M, Funakoshi H, Takahashi H, Hayakawa T, Mizuno S, Matsumoto K, Nakamura T.
    • Journal Title

      Mol Brain 2

      Pages: 8-23

    • Peer Reviewed
  • [Journal Article] Reciprocal regulation of IL-6 and Il-10 balance by HGF via recruitment of HO-1 in macrophages for attenuation of hepatic injury in a mouse model of endotoxemia.2009

    • Author(s)
      Kamimoto M, Mizuno S, Nakamura T.
    • Journal Title

      Int J Mol Med 24

      Pages: 161-170

    • Peer Reviewed
  • [Journal Article] Hepatocyte growth factor prevents multiple organ injuries in endotoxemic mice through a heme oxygenase-dependent mechanism.2009

    • Author(s)
      Kamimoto M, Mizuno S, Matsumoto K, Nakamura T.
    • Journal Title

      Biochem Biophys Res Communs 380

      Pages: 333-337

    • Peer Reviewed
  • [Journal Article] HGF, as a renotrophic and anti-fibrotic regulator in chronic renal disease.2008

    • Author(s)
      Mizuno S, Matsumoto K, Nakamura T.
    • Journal Title

      Front Biosci 13

      Pages: 7072-7086

    • Peer Reviewed
  • [Journal Article] The possible involvement of tensin2 in the expression and extension of nephrin by glomerular podocytes in mice.2008

    • Author(s)
      Kato T, Mizuno-S, Taketo MM, Kurosawa T.
    • Journal Title

      Biomed Res 29

      Pages: 279-287

    • Peer Reviewed
  • [Journal Article] Intranasal HGF administration ameriorates the physiological and morphological changes in lung emphysema,2008

    • Author(s)
      Hegab-AE, Kubo-H, Hayama-M, Asada-M, He-M, Mizuno-S, Nakamura-T.
    • Journal Title

      Mol Therapy 16

      Pages: 1417-1426

    • Peer Reviewed
  • [Journal Article] Inhibition of tubular cell proliferation by neutralizing endogenous HGF leads to renal hypoxia and bone marrow-derived cell engraftment in renal failure of mice.2008

    • Author(s)
      Ohnishi H, Mizuno S, Nakamura T.
    • Journal Title

      Am J Physiol 294

      Pages: F326-F335

    • Peer Reviewed
  • [Journal Article] Gelfand EW and Kanehiro A : Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice.2008

    • Author(s)
      Ito W, Tanimoto M, Ono K, Mizuno S, Yoshida A, Koga H, Fuchimoto Y, Kondo N, Tanimoto Y, Kiura K, Matsumoto K, Kataoka M, Nakamura T.
    • Journal Title

      Int Arch Allergy Immunol 145

      Pages: 324-339

    • Peer Reviewed
  • [Journal Article] Hepatocyte growth factor (HGF), an endogenous pulmotrophic regulator, for the rescue of acute and chronic lung diseases.

    • Author(s)
      Mizuno S, Ohnishi H, Nakamura T.
    • Journal Title

      Cell Signaling Transduction Therapy in press

    • Peer Reviewed
  • [Journal Article] Hepatocyte growth factor (HGF) for a cell-signal-based therapy during acute and chronic liver diseases.

    • Author(s)
      Oka K, Fukuta K, Mizuno S.
    • Journal Title

      Cell Signaling Transduction Therapy. in press

    • Peer Reviewed
  • [Presentation] 骨髄由来DCの遊走およびサイトカイン産生に対するHGFの調節作用2010

    • Author(s)
      大西浩之, 岡清政, 水野信哉, 中村敏一
    • Organizer
      第83回日本生化学学会
    • Place of Presentation
      神戸市
    • Year and Date
      2010-12-08
  • [Presentation] 急性腎不全マウスモデルでの病態進展に伴うHGF標的細胞の変遷とその意義2010

    • Author(s)
      水野信哉, 大西浩之, 神元幸, 中村敏一
    • Organizer
      第83回日本生化学学会
    • Place of Presentation
      神戸市
    • Year and Date
      2010-12-07
  • [Presentation] リコビナントヒトHGFは免疫複合体の沈着を介して健常ラットに蛋白尿を惹起する2010

    • Author(s)
      水野信哉, 池渕文彩, 福田一弘, 加藤貴史, 安達喜一, 松本邦夫, 中村敏一
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      広島市
    • Year and Date
      2010-03-18
  • [Presentation] 内因性HGFによる胆管上皮細胞の代償性成長を介した胆管硬化症の進展制御機構の解析2009

    • Author(s)
      水野信哉、中村敏一
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸市
    • Year and Date
      2009-10-23
  • [Presentation] 培養マクロファージを用いたHGFによるHMGB1放出抑制とその分子機構の解析2009

    • Author(s)
      神元幸、水野信哉、中村敏一
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸市
    • Year and Date
      2009-10-23
  • [Presentation] HGFによるカテプシンLの誘導抑制とその意義:糸球体傷害モデルを用いた解析2009

    • Author(s)
      加藤貴史、水野信哉、中村敏一
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸市
    • Year and Date
      2009-10-23
  • [Presentation] 敗血症マウスにおけるHGFによる急性肺傷害の発症阻止とその分子基盤2009

    • Author(s)
      神元幸、水野信哉、中村敏一
    • Organizer
      第8回日本再生医療学会
    • Place of Presentation
      東京都
    • Year and Date
      2009-03-05
  • [Presentation] HGFによるポドサイトでのネフリン発現増強を介した蛋白尿発症制御2009

    • Author(s)
      加藤貴史、水野信哉、中村敏一
    • Organizer
      第8回日本再生医療学会
    • Place of Presentation
      東京都
    • Year and Date
      2009-03-05
  • [Presentation] HGFによるマクロファージでの翻訳後修飾を介したHO-1誘導促進とその生理的意義2008

    • Author(s)
      神元幸、水野信哉、中村敏一
    • Organizer
      第81回日本生化学会大会.第31回日本分子生物学会年会合同大会
    • Place of Presentation
      神戸市
    • Year and Date
      20081211-20081212
  • [Presentation] HGFによるポドサイトの機能促進を介した蛋白尿制御機構2008

    • Author(s)
      加藤貴史、水野信哉、中村敏一
    • Organizer
      第81回日本生化学会大会.第31回日本分子生物学会年会合同大会
    • Place of Presentation
      神戸市
    • Year and Date
      2008-12-10
  • [Book] Gene Therapy for HGF Supplementation in the Rescue of Intractable Diseases. In "Gene Therapy : Types, Vectors and Developments".

    • Author(s)
      Mizuno-S, Nakamura-T.
    • Publisher
      NOVA Science Publisher, Hauppauge.(New York)(in press)
  • [Book] Hepatocyte growth factor (HGF) : Cardiotrophic roles and potential therapeutics for cardio.ascular disease. In : "Coronary Stent Restenosis".

    • Author(s)
      Mizuno S, Nakamura T.
    • Publisher
      Edited Ion Tintoiuin(in press)

URL: 

Published: 2012-01-26   Modified: 2016-04-21  

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