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Possible involvement of epigenomic alterations in the development of bronchial smooth muscle hyperresponsiveness in allergic asthma

Research Project

Project/Area Number 15K08248
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionHoshi University

Principal Investigator

Chiba Yoshihiko  星薬科大学, 薬学部, 教授 (00287848)

Co-Investigator(Renkei-kenkyūsha) Sakai HIROYASU  星薬科大学, 薬学部, 准教授 (00328923)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsアレルギー性喘息 / 気道過敏性 / 気管支平滑筋 / RhoA / microRNA (miRNA) / long non-coding RNA / lncRNA / 気管支喘息 / 複数世代抗原暴露
Outline of Final Research Achievements

The current study was performed to identify epigenetic changes associated with the pathogenesis of airway hyperresponsiveness (AHR) in asthma. In bronchial smooth muscles (BSMs) of mice with asthma, a BSM hyperresponsiveness with an up-regulation of RhoA protein was observed. The RhoA up-regulation induced by antigen tended to be augmented in BSMs of the F3 generation compared to those of the parents. A MeDIP-Seq analysis revealed 93 differentially methylated regions of CpG islands between the diseased and control BSMs. However, no change in the CpG methylation of RhoA gene was observed. Microarray analyses revealed 14 and 131 differentially expressed miRNAs and lncRNAs, respectively, in BSMs of the diseased mice. Some of the ncRNAs that might be associated with RhoA translation are also differentially expressed. These findings suggest that wide variety of epigenetic changes, including changes in functional ncRNA expression, in the BSMs are involved in the development of AHR in asthma.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2018 2017 2016 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (8 results) Remarks (2 results)

  • [Journal Article] Intranasal administration of recombinant progranulin inhibits bronchial smooth muscle hyperresponsiveness in mouse allergic asthma.2018

    • Author(s)
      Chiba Y, Danno S, Suto R, Suto W, Yamane Y, Hanazaki M, Katayama H, Sakai H.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol.

      Volume: 314

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-17A directly acts on bronchial smooth muscle cells and augments the contractility.2017

    • Author(s)
      Chiba Y, Tanoue G, Suto R, Suto W, Hanazaki M, Katayama H, Sakai H.
    • Journal Title

      Pharmacol. Rep.

      Volume: 69 Pages: 377-385

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 喘息モデルマウスの気道局所における脂肪酸代謝変化の網羅的解析2018

    • Author(s)
      土山実紗規、須藤 航、竹澤菜穂美、原田梨香、藤原実来、花崎元彦、片山 浩、岩崎雄介、酒井寛泰、千葉義彦
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウスアレルギー性喘息時の過敏性気管支平滑筋におけるMalat1発現の増加2018

    • Author(s)
      安達幸佳、藤井茂基、須藤 航、花崎元彦、片山 浩、酒井寛泰、千葉義彦
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 気道過敏性時の気管支平滑筋収縮反応亢進における Rac1 signaling の関与2017

    • Author(s)
      甲斐 友規, 千葉 義彦, 里 史明, 湯本 哲郎, 酒井 寛泰
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス気管支平滑筋のlow pH誘発収縮抑制反応におけるPGE2の関与2017

    • Author(s)
      山根 大和, 須藤 航, 岩崎 雄介, 酒井 寛泰, 千葉 義彦
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] マウスアレルギー性喘息時の過敏性気管支平滑筋における発現変動遺伝子の網羅的解析2017

    • Author(s)
      須藤 航, 安達 幸佳, 山根 大和, 佐藤 翼, 岩崎 雄介, 酒井 寛泰, 亀井 淳三,, 千葉 義彦
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] マウスアレルギー性喘息時の過敏性気管支平滑筋におけるlong noncoding RNAs発現の変化2017

    • Author(s)
      千葉 義彦, 安達 幸佳, 須藤 航, 山根 大和, 花崎 元彦, 片山 浩, 酒井 寛泰
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Presentation] 抗原誘発喘息マウスの気管支平滑筋過敏性発現におけるprostaglandin D2 (PGD2) の関与2017

    • Author(s)
      須藤 航、佐藤 翼、片山 浩、花崎元彦、酒井寛泰、千葉義彦
    • Organizer
      第59回日本平滑筋学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 喘息マウスの気管支平滑筋におけるRhoA発現に及ぼす複数世代抗原曝露の影響2016

    • Author(s)
      千葉義彦、太田康介、多田沙織、川田 朋、須藤 航、岩崎雄介、酒井寛泰、花崎元彦、片山 浩
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Remarks] 星薬科大学ホームページ

    • URL

      http://www.hoshi.ac.jp/site/index.php

    • Related Report
      2017 Annual Research Report
  • [Remarks]

    • URL

      http://polaris.hoshi.ac.jp/kyoshitsu/sogokiso/index.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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