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Properties of steroidogenesis, M1/M2 polarization, and adhesion to niche-forming cells in tissue-resident macrophages

Research Project

Project/Area Number 19K06406
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionOsaka Prefecture University

Principal Investigator

Ogawa Kazushige  大阪府立大学, 生命環境科学研究科, 教授 (60231221)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords組織在住マクロファージ / 精巣間質マクロファージ / 肺間質マクロファージ / クッパー細胞 / ニッチ / プロゲステロン / Eph / ephrin / 精巣マクロファージ / 卵巣マクロファージ / 性ステロイド / M1 / M2 / 常在マクロファージ / 器官特異生 / 組織定着機構 / 分極化 / M1分極化 / M2分極化 / ホーミング / 定着機構
Outline of Research at the Start

病態とマクロファージ(Mφ)の分極化(炎症性のM1と抗炎症性のM2型)の研究は,単球由来の動員Mφを主体に進んでいる。Mφには,胎生期に食細胞が各器官に浸潤・定着し,器官特異的に分化した自己増殖する常在Mφも存在する。常在Mφの増殖培養は難しく,器官定着機構や炎症時の動態など不明な点が多い。本研究では,代表者が開発した「常在Mφの継代培養・増殖法(特開019-17291)」を活用し,常在Mφの臨床応用を究極の目的に,大量培養できた常在Mφを材料に,器官特異的性状,M1・M2型Mφへの分極化と両Mφの相互作用,器官定着機構とホーミング能を調べ,常在Mφの移植治療法開発の基盤となる研究を行う。

Outline of Final Research Achievements

Testicular interstitial macrophages, lung interstitial macrophages, and liver tissue-resident macrophages were successfully propagated by mixed culturing with the respective organ-specific stromal cells. It was newly found that (i) testicular interstitial macrophages expressed the androgen receptor and produced progesterone whose production was significantly upregulated by cAMP and a β adrenergic agonist, and downregulated by M1 polarization inducers; (ii) lung interstitial macrophages treated with the M1 polarization inducers induced to express iNOS (a typical marker of the M1 phenotype) and stably expressed arginase 1 (a typical marker of the M2 phenotype), which was constantly expressed at the steady-state, although recruited macrophages do not highly express both molecules at the same time; (iii) EphA/ephrin-A and EphB/ephrin-B molecular system induced to promote the adhesion of liver tissue-resident macrophages to the mimic surface of sinusoidal endothelial cells.

Academic Significance and Societal Importance of the Research Achievements

精巣間質マクロファージ(Mφ)のプロゲステロン(P4)産生は世界初の知見である。ライディッヒ細胞のテストステロン産生・分泌において精巣間質MφのP4を介した局所的な制御機構の存在が示唆されるため,精巣間質MφのP4産生制御は不妊治療のシーズになる。肺間質Mφは分化途中の肺胞Mφと考えられてきたため,研究は進んでいない。開発した方法では大量の肺間質Mφが得られるため,今後の研究への活用が期待できる。肝常在Mφの定着機構は不明であったが,EphA/ephrin-A,EphB/ephrin-Bシグナルを介する肝常在Mφ接着増強を見出した研究結果から,定着機構の一端が解明されたと考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (20 results)

All 2022 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (14 results)

  • [Journal Article] Testicular macrophages produce progesterone de novo promoted by cAMP and inhibited by M1 polarization inducers2022

    • Author(s)
      Sawako Yamauchi, Kousuke Yamamoto, Kazushige Ogawa
    • Journal Title

      Biomedicines

      Volume: 10(2) Pages: 1-22

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell properties of lung tissue-resident macrophages propagated by co-culture with lung fibroblastic cells from C57BL/6 and BALB/c mice2021

    • Author(s)
      Mayu Tsurutani, Haruka Horie, Kazushige Ogawa
    • Journal Title

      Biomedicines

      Volume: 9(9) Issue: 9 Pages: 1-23

    • DOI

      10.3390/biomedicines9091241

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression and localisation of ephrin-B1 and EphB4 in steroidogenic cells in the naturally cycling mouse ovary2021

    • Author(s)
      Jahagir Alam, Kazushige Ogawa
    • Journal Title

      Reproductive Biology

      Volume: 21(3) Issue: 3 Pages: 1-14

    • DOI

      10.1016/j.repbio.2021.100511

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression and localisation of ephrin-B1, EphB2, and EphB4 in the mouse testis during postnatal development2020

    • Author(s)
      Md Royhan Gofur, Jahagir Alam, Kazushige Ogawa
    • Journal Title

      Reproductive Biology

      Volume: 20 Issue: 3 Pages: 321-332

    • DOI

      10.1016/j.repbio.2020.06.001

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Simple propagation method for resident macrophages by co-culture and subculture, and their isolation from various organs2019

    • Author(s)
      K. Ogawa, M. Tsurutani, A. Hashimoto, M. Soeda
    • Journal Title

      BMC Immunology

      Volume: 20 Issue: 1 Pages: 1-13

    • DOI

      10.1186/s12865-019-0314-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Compartments with predominant ephrin-B1 and EphB2/B4 expression are present alternately along the excurrent duct system in the adult mouse testis and epididymis.2019

    • Author(s)
      M. R. Gofur, K. Ogawa
    • Journal Title

      Andrology

      Volume: 7 Issue: 6 Pages: 888-901

    • DOI

      10.1111/andr.12523

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 精巣組織在住マクロファージのプロゲステロン産生とその制御機構2022

    • Author(s)
      小川 和重,山内 佐和子
    • Organizer
      第127日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肺間質マクロファージの培養・増殖法と性状解析2022

    • Author(s)
      鶴谷 真悠,堀江 遼,小川 和重
    • Organizer
      第127日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 卵巣常在マクロファージの初代培養と性ステロイド産生能2021

    • Author(s)
      井上 美聖,Alam Jahagir,小川 和重
    • Organizer
      第164回日本獣医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 精巣常在マクロファージのプロゲステロン産生能2021

    • Author(s)
      山内 佐和子,小川 和重
    • Organizer
      第164回日本獣医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肺から培養・増殖させた肺間質マクロファージの性状解析2021

    • Author(s)
      堀江 遼,鶴谷 真悠,小川 和重
    • Organizer
      第164回日本獣医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Expression and localization of ephrin-B1 and EphB4 in steroidogenic cells in mouse ovaries2021

    • Author(s)
      Jahagir Alam, Kazushige Ogawa
    • Organizer
      第126回日本解剖学会全国学術集会 第98回日本生理学会大会 合同大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Expression and localization of ephrin-B1, EphB2 and EphB4 in the mouse testis during postnatal development2021

    • Author(s)
      Kazushige Ogawa, Md. Royhan Gofur, Jahagir Alam
    • Organizer
      第126回日本解剖学会全国学術集会 第98回日本生理学会大会 合同大会
    • Related Report
      2020 Research-status Report
  • [Presentation] クッパー細胞の接着分子,接着制御分子Eph,ephrinの発現と器官定着性2020

    • Author(s)
      古原 翔,小川和重
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Expression and localization of ephrin-B1, EphB2 and EphB4 in the mouse testis during postnatal development2020

    • Author(s)
      Md Royhan Gofur, Jahagir Alam, Kazushige Ogawa
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] クッパー細胞のEph,ephrin発現とEph/ephrinシグナルが接着に及ぼす影響2019

    • Author(s)
      古原 翔,山本皓介,小川和重
    • Organizer
      第162回日本獣医学会学術集会(つくば市)
    • Related Report
      2019 Research-status Report
  • [Presentation] 増殖・分離した精巣常在マクロファージの性状解析とステロイドホルモン産生能2019

    • Author(s)
      山本皓介,小川和重
    • Organizer
      第162回日本獣医学会学術集会(つくば市)
    • Related Report
      2019 Research-status Report
  • [Presentation] Expression and localization of ephrin-B1 and EphB4 in the mouse ovary2019

    • Author(s)
      J. Alam, K. Ogawa
    • Organizer
      第162回日本獣医学会学術集会(つくば市)
    • Related Report
      2019 Research-status Report
  • [Presentation] 精巣マクロファージの継代培養増殖・分離とステロイドホルモン産生能について2019

    • Author(s)
      小川和重,山本皓介
    • Organizer
      第95回日本解剖学会近畿支部学術集会(吹田市)
    • Related Report
      2019 Research-status Report
  • [Presentation] クッパー細胞のEph, ephrinシグナルが接着に及ぼす影響2019

    • Author(s)
      古原 翔,小川和重
    • Organizer
      第95回日本解剖学会近畿支部学術集会(吹田市)
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-12-25  

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