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Molecular mechanisms of ineffective hematopoiesis in myelodysplastic syndromes

Research Project

Project/Area Number 26461409
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionFukushima Medical University

Principal Investigator

Shikama Yayoi  福島県立医科大学, 医学部, 教授 (40291562)

Co-Investigator(Kenkyū-buntansha) 七島 勉  福島県立医科大学, 医学部, 博士研究員 (10192105)
野地 秀義  福島県立医科大学, 医学部, 准教授 (20347214)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords骨髄異形成症候群 / 好中球 / c-Fos / miR-34a / miR-155 / TNF-alpha / migration / 酸化ストレス / MDS / NF-kB / 遊走能 / TNFalpha / NF-kappaB / ERストレス
Outline of Final Research Achievements

We found that c-Fos was reduced via overexpression of miR-34a and miR-155 in neutrophils isolated from patients with myelodysplastic syndromes (MDS). The reduction of c-Fos, which inhibited binding of NF-kB p60 to the promotor region of TNF-alpha DNA, induced overexpression of TNF-alpha under inflammation or oxidative stress (Shikama et al, PLoS One, 2016). The overexpression of miR-34a and miR-155 interfered with expression of Cdc42-specific guanine nucleotide exchange factors DOCK8 and FGD4, and a Rho family member Rac1, resulting in impairment in migration of MDS neutrophils toward fMLP and IL-8 (Cao et al, J Immunol, 2017).

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (13 results)

All 2017 2016 2015 2014 Other

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Mechanisms of Impaired Neutrophil Migration by MicroRNAs in Myelodysplastic Syndromes.2017

    • Author(s)
      Cao M, Shikama Y, Kimura H, Noji H, Ikeda K, Ono T, Ogawa K, Takeishi Y, Kimura J
    • Journal Title

      J.Immunol.

      Volume: 198(5) Issue: 5 Pages: 1887-1899

    • DOI

      10.4049/jimmunol.1600622

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Reduction of c-Fos via Overexpression of miR-34a Results in Enhancement of TNF- Production by LPS in Neutrophils from Myelodysplastic Syndrome Patients.2016

    • Author(s)
      Shikama Y, Cao M, Ono T, Feng X, Noji H, Kimura H, Ogawa K, Suzuki Y, Ikeda K, Takeishi Y, Kimura J.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 8 Pages: e0158527-e0158527

    • DOI

      10.1371/journal.pone.0158527

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Mechanisms of impaired neutrophil migration by microRNAs in myelodysplastic syndromes2017

    • Author(s)
      Cao M, Shikama Y, Kimura H, Noji H, Ikeda K, OnoT, Ogawa K, Takeishi Y, KImura J.
    • Organizer
      第90回日本薬理学会
    • Place of Presentation
      長崎市
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mechanisms of attenuated migration of neutrophils in myelodysplastic syndromes2016

    • Author(s)
      Meiwan Cao, Yayoi Shikama, Hideo Kimura, Hideyoshi Noji, Kazuei Ogawa, Yasuchika Takeishi, Junko Kumura
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Excessive TNF-alpha production resulting from reduction of c-fos via aberrant expression of miR-34a in neutrophils from myelodysplastic syndrome patients.2015

    • Author(s)
      Yayoi Shikama, Maiwan Cao, Tomoyuki Ono, Kojun Yamakawa, Michiko Anzai, Xiaomin Feng, Kazuko Kuriyama, Shun Hiruta, Hideyoshi Noji, Hideo Kimura, Kazuei Ogawa, Kazuhiko Ikeda, Yasuchika Takeishi, Junko Kimura
    • Organizer
      57th ASH Annual Meeting and Esposition
    • Place of Presentation
      Orland, USA
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Impaired neutrophil migration resulting from miR-34a and miR-155 overexpressed in neutrophils from myelodysplastic syndrome patients.2015

    • Author(s)
      Meiwan Cao, Yayoi Shikama, Michiko Anzai, Junko Kimura
    • Organizer
      57th ASH Annual Meeting and Esposition
    • Place of Presentation
      Orland, USA
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Excessive TNFalpha production via reduced expression of c-Fos in neutrophils from myelodysplastic syndrome patients.2015

    • Author(s)
      Yayoi Shikama, Meiwan Cao, Kojun Yamakawa, Xiaomin Feng, Michiko Anzai, Tomoyuki Ono, Hideyoshi Noji, Kazuei Ogawa, Yuko Suzuki, Hideo Kimura, Yasuchika Takeishi, Junko Kimura
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢市
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 酸化ストレス下のTNF-α産生に対するc-fosの抑制作用2015

    • Author(s)
      橋本舞、色摩弥生、安斎美智子、木村純子
    • Organizer
      第66回日本薬理学会北部会
    • Place of Presentation
      富山市
    • Year and Date
      2015-09-18
    • Related Report
      2015 Research-status Report
  • [Presentation] miR-34a and miR-155 overexpression suppresses neutrophil migration and activation of Cdc422015

    • Author(s)
      曹美婉、色摩弥生、木村純子
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-03-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Effects of miR-34a/miR-155-mediated c-Fos reduction on TNF production in myelodysplastic syndromes2014

    • Author(s)
      色摩弥生、曹美婉、山川幸純、馮暁敏、安斎美知子、小野委成、野地秀義、小川一英、鈴木裕子、木村秀夫、竹石恭知、木村純子
    • Organizer
      第76回日本血液学学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31
    • Related Report
      2014 Research-status Report
  • [Presentation] Effects of miR-34a and miR-155 overexpression on neutrophil functions2014

    • Author(s)
      曹美婉、色摩弥生、木村純子
    • Organizer
      第56回日本薬理学会北部会
    • Place of Presentation
      福島市
    • Year and Date
      2014-09-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Approach to pathogenesis of myelodysplastic syndromes via aberrant gene expression in neutrophils2014

    • Author(s)
      色摩弥生
    • Organizer
      筑波大学 北アフリカ研究センター 研究室セミナー
    • Place of Presentation
      筑波市
    • Year and Date
      2014-07-25
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] 研究成果情報・学会等表彰 (研究成果)

    • URL

      http://www.fmu.ac.jp/univ/kenkyu/kenkyuseika/seika/1612.html

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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