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siRNA for the treatment of airway remodeling

Research Project

Project/Area Number 22590859
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionMie University

Principal Investigator

KOBAYASHI Tetsu  三重大学, 医学部附属病院, 講師 (20437114)

Co-Investigator(Kenkyū-buntansha) TAGUCHI Osamu  三重大学, 医学系研究科, 准教授 (00293770)
田口 修  三重大学, 医学(系)研究科(研究院), 准教授 (90197244)
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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肺線維症 / siRNA / RNAi / TGF-β / リモデリング / 線維芽細胞
Research Abstract

SiRNA has been the focus of attention for its potential application for the development of new drugs.To evaluate the effect of intratracheal administration of siRNAs in murine disease models. Firstly, bleomycin was used for induction of lung fibrosis. After confirming the effectiveness of siRNA effect in vitro, siRNAs for several targets including TGF-beta1 were intratracheally administered by inhalation. Mice treated with scrambled siRNA or vehicle were used as controls. We generated a novel model of human TGF-beta1 transgenic mouse that spontaneously develops pulmonary fibrosis. Intrapulmonary delivery of aerosolized siRNAs of TGF-beta1 significantly inhibited bleomycin-induced pulmonary fibrosis. In addition, aerosolized siRNAs against human TGF-beta1 also inhibited spontaneous pulmonary fibrosis.These results suggest that intratracheal instillation of RNAi agents may be useful for the therapy of airway remodeling.

Report

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

    (19 results)

All 2012 2011 2010

All Journal Article (11 results) (of which Peer Reviewed: 10 results) Presentation (6 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Efficacy of a novel class of RNA interference therapeutic agents2012

    • Author(s)
      Hamasaki T, Suzuki H, Shirohzu H, Matsumoto T, D'Alessandro-Gabazza CN,Gil-Bernabe P, Boveda-Ruiz D, Naito M, Kobayashi T, Toda M, Mizutani T, TaguchiO, Morser J, Eguchi Y, Kuroda M, Ochiya T, Hayashi H, Gabazza EC, Ohgi T
    • Journal Title

      PLoS One

      Volume: 7 Issue: 8 Pages: 1-15

    • DOI

      10.1371/journal.pone.0042655

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Correlation between circulating fibrocytes, and activity andprogression of interstitial lung diseases2012

    • Author(s)
      Fujiwara A, Kobayashi H, Masuya M, Maruyama M, Nakamura S, Ibata H, FujimotoH, Ohnishi M, Urawa M, Naito M, Takagi T, Kobayashi T, Gabazza EC, Takei Y,Taguchi O
    • Journal Title

      Respirology

      Volume: 17 Issue: 4 Pages: 693-8

    • DOI

      10.1111/j.1440-1843.2012.02167.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of thrombin-activatablefibrinolysis inhibitor in allergic bronchial asthma2012

    • Author(s)
      Fujiwara A, Taguchi O, Takagi T, D'Alessandro-Gabazza CN, Boveda-Ruiz D, Toda M, Yasukawa A, Matsushima Y, Miyake Y, Kobayashi H, Kobayashi T, Gil-Bernabe P,Naito M, Yoshida M, Morser J, Takei Y, Gabazza EC.
    • Journal Title

      Lung

      Volume: 190 Pages: 189-98

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development and preclinical efficacy of novel transforming growthfactor-β1 short interfering RNAs for pulmonary fibrosis2012

    • Author(s)
      D'Alessandro-Gabazza CN, Kobayashi T, Boveda-Ruiz D, Takagi T, Toda M,Gil-Bernabe P, Miyake Y, Yasukawa A, Matsuda Y, Suzuki N, Saito H, Yano Y, Fukuda A, Hasegawa T, Toyobuku H, Rennard SI, Wagner PD, Morser J, Takei Y, Taguchi O, Gabazza EC
    • Journal Title

      Am J Respir Cell MolBiol

      Volume: 46 Pages: 397-406

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 呼吸器疾患に対するsiRNA創薬の進歩2012

    • Author(s)
      小林哲
    • Journal Title

      分子呼吸器病

      Volume: 16 Pages: 91-93

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Inhibition of allergicbronchial asthma by thrombomodulin is mediated by dendritic cells2011

    • Author(s)
      Takagi T, Taguchi O, Toda M, Ruiz DB, Bernabe PG, D'Alessandro-Gabazza CN,Miyake Y, Kobayashi T, Aoki S, Chiba F, Yano Y, Conway EM, Munesue S, Yamamoto Y,Yamamoto H, Suzuki K, Takei Y, Morser J, Gabazza EC
    • Journal Title

      Am J RespirCrit Care Med

      Volume: 183 Pages: 31-42

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of allergic bronchial asthma by thrombomodulin is mediated by dendritic cells2011

    • Author(s)
      高木健裕
    • Journal Title

      American journal of respiratory and critical care medicine

      Volume: 183 Issue: 1 Pages: 31-31

    • DOI

      10.1164/rccm.201001-0107oc

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development and Preclinical Efficacy of Novel Transforming Growth Factor-β1 siRNAs for Pulmonary Fibrosis2010

    • Author(s)
      Corina N D'Alessandro-Gabazza
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: (掲載確定) Issue: 3 Pages: 397-406

    • DOI

      10.1165/rcmb.2011-0158oc

    • Related Report
      2012 Annual Research Report 2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic growth factor (HGF) inhibits cigarette smoke extract induced apoptosis in human bronchial epithelial cells.2010

    • Author(s)
      Togo S, Sugiura H, Nelson A, Kobayashi T, et al.
    • Journal Title

      Exp Cell Res.

      Volume: 316 Pages: 3501-11

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] What has been learnt from the thrombin-activatable fibrinolysis inhibitor-deficient mouse?2010

    • Author(s)
      Morser J, Gabazza EC, Myles T, Leung LL.
    • Journal Title

      J Thromb Haemost.

      Volume: 8 Pages: 868-76

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphoinositide 3-kinase induced activation and cytoskeletal translocation of Protein kinase CK2 in protease activated receptor 1-stimulated platelets.2010

    • Author(s)
      Nakanishi K, Toyoda H, Tanaka S, Yamamoto H, Komada Y, Gabazza E C, et al.
    • Journal Title

      Thromb Res.

      Volume: 126 Pages: 511-6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 気道リモデリング制御方法としてのRNAi創薬の試み2012

    • Author(s)
      小林 哲
    • Organizer
      臨床喘息研究会 第20回学術講演会
    • Place of Presentation
      金沢
    • Year and Date
      2012-10-06
    • Related Report
      2012 Final Research Report
  • [Presentation] 呼吸器疾患におけるRNAiを用いた治療の可能性2012

    • Author(s)
      小林 哲
    • Organizer
      第85回閉塞性肺疾患研究会
    • Place of Presentation
      東京
    • Year and Date
      2012-07-21
    • Related Report
      2012 Final Research Report
  • [Presentation] 気道リモデリングにおけるメカニカルストレスの関与の検討2012

    • Author(s)
      小林 哲
    • Organizer
      第84回閉塞性肺疾患研究会
    • Place of Presentation
      東京
    • Year and Date
      2012-01-28
    • Related Report
      2012 Final Research Report
  • [Presentation] 気道リモデリングにおける新規創薬の試み2011

    • Author(s)
      小林哲
    • Organizer
      アレルギー気道上皮細胞研究会第15回学術大会
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-12-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 気道リモデリングにおけるECM contraction および degradationの検討2011

    • Author(s)
      小林 哲
    • Organizer
      第19回学術講演会
    • Place of Presentation
      大阪
    • Year and Date
      2011-11-19
    • Related Report
      2012 Final Research Report
  • [Presentation] 呼吸器疾患に対するsiRNA創薬の可能性2010

    • Author(s)
      小林哲, 他
    • Organizer
      アレルギー気道上皮細胞研究会
    • Place of Presentation
      シェーンバッハ・サボー(東京)
    • Year and Date
      2010-12-04
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 線維症予防又は治療剤2010

    • Inventor(s)
      小林哲, ガバザエス テバン
    • Industrial Property Rights Holder
      三重大学大塚製薬
    • Industrial Property Number
      2010-231946
    • Filing Date
      2010-10-14
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 線維症予防又は治療剤2010

    • Inventor(s)
      小林哲, ガパザエステバン, 他
    • Industrial Property Rights Holder
      三重大学大塚製薬
    • Industrial Property Number
      2010-231946
    • Filing Date
      2010-10-14
    • Related Report
      2010 Annual Research Report

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

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