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Elucidation of the roles of zinc released from mast cells in wound healing

Research Project

Project/Area Number 16K15152
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Environmental and hygienic pharmacy
Research InstitutionSuzuka University of Medical Science

Principal Investigator

NISHIDA KEIGO  鈴鹿医療科学大学, 薬学部, 准教授 (80360618)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords亜鉛 / 皮膚創傷治癒 / マスト細胞 / 亜鉛トランスポーター / サイトカイン / 褥瘡 / 創傷治癒
Outline of Final Research Achievements

Mast cell granules contain high levels of zinc which is released upon degranulation. However, its physiological roles and the mechanism of release have not been clear. Therefore, we aimed to elucidate the mechanism of zinc uptake into mast cell granules and the role of extracellularly released zinc.
We identified the zinc transporter ZnT2 as a molecule involved in intragranular uptake of zinc in mast cells. In ZnT2-deficient mast cells, stimulation-dependent zinc release was not observed. Knocking ZnT2 in mice caused delayed wound healing. Overall, we showed a new physiological significance of zinc released from mast cells.

Academic Significance and Societal Importance of the Research Achievements

亜鉛補充療法が有効な疾患がいくつか知られている。例えば、長期入院患者や在宅で介護を受けている老人においてばしば観察される褥瘡などである。しかしながら、皮膚における創傷治癒において、亜鉛の作用機序に関しては十分に理解されていないのが現状である。今回の研究結果より、マスト細胞からの放出亜鉛が皮膚創傷治癒の炎症相を制御している可能性を示した。以上の知見は、亜鉛を用いた効率の良い治療法の開発や入院患者で問題となっている褥瘡の予防・治療に役立つ可能性が示された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (25 results)

All 2019 2018 2017 2016

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Invited: 1 results)

  • [Journal Article] L-Type Calcium Channel-Mediated Zinc Wave Is Involved in the Regulation of IL-6 by Stimulating Non-IgE with LPS and IL-33 in Mast Cells and Dendritic Cells2019

    • Author(s)
      Uchida Ryota、Xiang Huihui、Arai Hiroya、Kitamura Hidemitsu、Nishida Keigo
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 1 Pages: 87-93

    • DOI

      10.1248/bpb.b18-00565

    • NAID

      130007542207

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-01-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of the minimal region of peptide derived from ADP-ribosylation factor1 (ARF1) that inhibits IgE-mediated mast cell activation2019

    • Author(s)
      Uchida Ryota、Egawa Tomonori、Fujita Yoshio、Furuta Kazuyuki、Taguchi Hiroaki、Tanaka Satoshi、Nishida Keigo
    • Journal Title

      Molecular Immunology

      Volume: 105 Pages: 32-37

    • DOI

      10.1016/j.molimm.2018.11.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of Toll-like Receptor 7/8 Agonist Amino Acid for Antigen-Adjuvant Conjugation Co-delivery System2018

    • Author(s)
      Fujita Yoshio, Uchida Ryota, Nishida Keigo, Taguchi Hiroaki
    • Journal Title

      Journal of Targeted Drug Delivery

      Volume: 1 Pages: 1-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Zinc Signaling in the Regulation of Mast Cell-, Basophil-, and T Cell-Mediated Allergic Responses2018

    • Author(s)
      Nishida Keigo、Uchida Ryota
    • Journal Title

      Journal of Immunology Research

      Volume: 2018 Pages: 1-9

    • DOI

      10.1155/2018/5749120

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 亜鉛による皮膚創傷治癒の制御機構2018

    • Author(s)
      西田 圭吾、内田 亮太
    • Journal Title

      Farumashia

      Volume: 54 Issue: 7 Pages: 675-679

    • DOI

      10.14894/faruawpsj.54.7_675

    • NAID

      130007386947

    • ISSN
      0014-8601, 2189-7026
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] マスト細胞からの亜鉛による皮膚創傷治癒の制御機構2018

    • Author(s)
      西田圭吾、内田亮太
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 69 Pages: 264-270

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frontiers in Researches of Allergy2017

    • Author(s)
      Nishida K and Kashiwakura JI
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 137 Issue: 5 Pages: 493-494

    • DOI

      10.1248/yakushi.16-00239-F

    • NAID

      130005631398

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2017-05-01
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulatory Mechanism of Mast Cell Activation by Zinc Signaling2017

    • Author(s)
      Nishida K and Uchida R
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 137 Issue: 5 Pages: 495-501

    • DOI

      10.1248/yakushi.16-00239-1

    • NAID

      130005631394

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2017-05-01
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between itching and the serum zinc levels in patients with varicose veins2017

    • Author(s)
      Takai Y, Hiramoto K, Nishimura Y, Uchida R, Nishida K and Ooi K
    • Journal Title

      Journal of Pharmaceutical Health Care and Sciences

      Volume: 3 Issue: 1

    • DOI

      10.1186/s40780-017-0092-9

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metallothioneins are required for human basophil interleukin-4 gene induction via FcεRΙ stimulation2016

    • Author(s)
      Ugajin T, Shibama S, Nishida K, Yokozeki H.
    • Journal Title

      Allergology International

      Volume: 65 Issue: 4 Pages: 466-468

    • DOI

      10.1016/j.alit.2016.03.005

    • NAID

      130005431297

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyperactivation of JAK1 tyrosine kinase induces stepwise, progressive pruritic dermatitis2016

    • Author(s)
      Yasuda T, Fukada T, Nishida K, Nakayama M, Matsuda M, Miura I, Dainichi T, Fukuda S, Kabashima K, Nakaoka S, Bin BH, Kubo M, Ohno H, Hasegawa T, Ohara O, Koseki H, Wakana S, Yoshida H
    • Journal Title

      J. Clin. Invest

      Volume: 126(6) Issue: 6 Pages: 2064-76

    • DOI

      10.1172/jci82887

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 6-(4-Amino-2-butyl-imidazoquinolyl)-norleucine: Toll-like Receptor 7 and 8 Agonist Amino Acid for Self-Adjuvanting Peptide Vaccine2016

    • Author(s)
      Fujita Y, Hirai K, Nishida K, Taguchi H
    • Journal Title

      Amino Acids.

      Volume: 48 Issue: 5 Pages: 1319-1329

    • DOI

      10.1007/s00726-016-2190-7

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] TLRおよびサイトカイン受容体シグナル経路における亜鉛ウェーブの役割2018

    • Author(s)
      内田亮太、西田圭吾
    • Organizer
      第6回 メタロミクス研究フォーラム プラズマ分光分析研究会 第104回講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 亜鉛は亜鉛受容体GPR39を介してサイトカイン産生を促すはたらきを持つ2018

    • Author(s)
      内田亮太、西田圭吾
    • Organizer
      第64回 日本薬学会東海支部会総会 大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 二重標的化したペプチドワクチンの開発研究2018

    • Author(s)
      藤田快男、西田圭吾、田口博明
    • Organizer
      第64回 日本薬学会東海支部会総会 大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 下肢静脈瘤患者における掻痒は血清亜鉛の低下と関係する2018

    • Author(s)
      高井靖、西村善幸、西田圭吾、大井一弥
    • Organizer
      医療薬学ファーラム2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] Toll様受容体およびサイトカイン受容体のシグナル経路における亜鉛ウェーブの役割2018

    • Author(s)
      内田亮太、新井裕也、西田圭吾
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 亜鉛シグナルによるLPS誘導性のサイトカイン転写制御2017

    • Author(s)
      内田亮太、西田圭吾
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部 合同学術大会2017
    • Related Report
      2017 Research-status Report
  • [Presentation] STAP-2 negatively controls FceRI-mediated mast cell activation2017

    • Author(s)
      Kyosuke Inui, Junichi Kashiwakura, Keigo Nishida, Yuichi Sekine, Kodai Saitoh, Ryuta Muromoto, Yuichi Kitai, Akihiko Yoshimura, Kenji Oritani, Tadashi Matsuda
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 柑橘類「新姫」果実成分の生体機能に及ぼす効果の解析2017

    • Author(s)
      鈴木宏冶、佐藤英介、西田圭吾、西岡淳二
    • Organizer
      第15回 日本機能性食品医用学会 総会
    • Related Report
      2017 Research-status Report
  • [Presentation] L型カルシウムチャネル遮断薬のサイトカイン産生抑制効果2017

    • Author(s)
      内田亮太、西田圭吾
    • Organizer
      第63回 日本薬学会東海支部会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] マスト細胞におけるARFペプチドの抗アレルギー効果の構造活性相関2017

    • Author(s)
      内田亮太、西田圭吾
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Research-status Report
  • [Presentation] マスト細胞から放出される亜鉛は皮膚創傷治癒に関与する2016

    • Author(s)
      西田圭吾、内田亮太
    • Organizer
      第65回 日本アレルギー学会学術大会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 細胞内亜鉛シグナルにおける亜鉛イオンのターゲット分子の検索2016

    • Author(s)
      内田亮太、西田圭吾
    • Organizer
      第62回 日本薬学会東海支部会総会大会
    • Place of Presentation
      愛知学院大学楠元キャンパス(愛知)
    • Related Report
      2016 Research-status Report
  • [Presentation] TLR7/8活性化能を有する免疫自己賦活型インフルエンザワクチンの開発2016

    • Author(s)
      藤田快男、平井一行、西田圭吾、田口博明
    • Organizer
      第62回 日本薬学会東海支部会総会大会
    • Place of Presentation
      愛知学院大学楠元キャンパス(愛知)
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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