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Mechanism of protein secretion by physical stimuli (turbulent) and its physiological significance

Research Project

Project/Area Number 20K21523
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionShiga University of Medical Science

Principal Investigator

Nishi Eiichiro  滋賀医科大学, 医学部, 教授 (30362528)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsナルディライジン / 物理刺激 / タンパク質分泌 / 血小板 / ペプチダーゼ / タンパク分泌
Outline of Research at the Start

生体内においてあらゆる細胞は、周囲の環境から圧力、張力、浸透圧や温度などの物理的刺激を受けている。最近我々は、物理刺激のひとつである乱流がiPS細胞由来巨核球から血小板産生を促進すること、乱流刺激によりナルディライジン(NRDC)という酵素タンパク質の分泌が増えることを明らかにした。本研究では、乱流によって誘導される「NRDC分泌」と「血小板産生」という2つの事象の因果関係、NRDCの酵素活性の血小板産生における役割を明らかにする。

Outline of Final Research Achievements

Physical stimuli such as pressure, shear stress, and temperature are spatiotemporally regulated in vivo and are presumably involved in various homeostasis. We have shown that turbulent induces nardilysin (NRDC) secretion from iPS cell-derived megakaryocytes (imMKCL) and that NRDCs induce platelet production in a peptidase activity-dependent manner (Cell 2018). To clarify the causal relationship between turbulent-induced NRDC secretion and platelet production and the mechanism by which the peptidase activity contributes, we have generated NRDC-deficient imMKCL, megakaryocyte-specific NRDC-deficient mice and peptidase-inactive Nrdc knock-in mice, and examined the process of platelet production.

Academic Significance and Societal Importance of the Research Achievements

体内の細胞は、常に温度や圧力などの物理的刺激を受けています。これらの刺激を感知する受容体の発見に対して、2021年にノーベル医学生理学賞が授与されましたが、物理的刺激の生理病理学的役割はまだよくわかっていません。私たちは、物理的刺激のひとつである乱流が、NRDCというタンパク質の分泌を増やし、その結果血小板の産生が増えることを見出しました。本研究は、そのくわしいしくみを明らかにし、ひいては血小板減少症の治療につなげることを目的にして行いました。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report

Research Products

(28 results)

All 2022 2021 2020 Other

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (16 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Glycaemia and body weight are regulated by sodium-glucose cotransporter 1 (SGLT1) expression via O-GlcNAcylation in the intestine2022

    • Author(s)
      Nishimura Kimihiro、Fujita Yukihiro、Ida Shogo、Yanagimachi Tsuyoshi、Ohashi Natsuko、Nishi Kiyoto、Nishida Atsushi、Iwasaki Yasumasa、Morino Katsutaro、Ugi Satoshi、Nishi Eiichiro、Andoh Akira、Maegawa Hiroshi
    • Journal Title

      Molecular Metabolism

      Volume: 59 Pages: 101458-101458

    • DOI

      10.1016/j.molmet.2022.101458

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nardilysin in adipocytes regulates UCP1 expression and body temperature homeostasis2022

    • Author(s)
      Saijo S, Ohno M, Iwasaki H, Matsuda S, Nishi K, Hiraoka Y, Ide N, Kimura T, Nishi E.
    • Journal Title

      Scientific reports

      Volume: 12 Pages: 3449-3449

    • DOI

      10.1038/s41598-022-07379-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke.2021

    • Author(s)
      Hiwasa T, Wang H, Iwadate Y. et al
    • Journal Title

      BMC Med.

      Volume: 19 Pages: 131-131

    • DOI

      10.1186/s12916-021-02001-9

    • NAID

      120007132378

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MicroRNA-494-3p inhibits formation of fast oxidative muscle fibres by targeting E1A-binding protein p300 in human-induced pluripotent stem cells2021

    • Author(s)
      Iwasaki Hirotaka、Ichihara Yoshinori、Morino Katsutaro、Lemecha Mengistu、Sugawara Lucia、Sawano Tatsuya、Miake Junichiro、Sakurai Hidetoshi、Nishi Eiichiro、Maegawa Hiroshi、Imamura Takeshi
    • Journal Title

      Scientific Reports

      Volume: 11 Pages: 1161-1161

    • DOI

      10.1038/s41598-020-80742-y

    • NAID

      120006953800

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deficiency of Nardilysin in the Liver Reduces Serum Cholesterol Levels2021

    • Author(s)
      Yasuda Daisuke、Hiraoka Yoshinori、Ohno Mikiko、Nishi Kiyoto、Iwasaki Hirotaka、Kita Toru、Nishi Eiichiro、Kume Noriaki
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 44 Issue: 3 Pages: 363-371

    • DOI

      10.1248/bpb.b20-00722

    • NAID

      130007993442

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nardilysin controls cardiac sympathetic innervation patterning through regulation of p75 neurotrophin receptor.2020

    • Author(s)
      Ohno M, Nishi K, Hiraoka Y, Niizuma S, Matsuda S, Iwasaki H, Kimura K, and Nishi E
    • Journal Title

      FASEB Journal

      Volume: 34 Issue: 9 Pages: 11624-11640

    • DOI

      10.1096/fj.202000604r

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association between serum anti-ASXL2 antibody levels and acute aschemic stroke, acute myocardial infarction, diabetes mellitus, chronic kidney disease and digestive organ cancer, and their possible association with atherosclerosis and hypertension.2020

    • Author(s)
      Li SY, Yoshida Y, Kobayashi E, Adachi A, Iwadate Y, et al.
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 46 Pages: 1274-1288

    • DOI

      10.3892/ijmm.2020.4690

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elevated levels of autoantibodies against DNAJC2 in sera of patients with atherosclerotic diseases2020

    • Author(s)
      Yoshida Y, Zhang XM, Wang H, Machida T, Iwadate Y, et al.
    • Journal Title

      Heliyon

      Volume: 6

    • DOI

      10.1016/j.heliyon.2020.e04661

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum anti-LRPAP 1 is a common biomarker for digestive organ cancers and atherosclerotic diseases2020

    • Author(s)
      Sumazaki M, Shimada H, Ito M, Shiratori F, Iwadate Y, et al.
    • Journal Title

      Cancer Science

      Volume: 111 Pages: 4453-4464

    • DOI

      10.1111/cas.14652

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 多機能プロテアーゼによる心拍数制御機構2021

    • Author(s)
      大野 美紀子, 松浦 博, 牧山 武, 糀谷 泰彦, 西 清人, 岩崎 広高, 松田 真太郎, 木村 剛, 西 英一郎
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ナルディライジンによる核内受容体ROR/REV-ERB活性調節機構2021

    • Author(s)
      平岡義範、古市真唯、鎌田真由子、斉藤沙樹、久米典昭、吉種光、深田吉孝、池田正明、西英一郎
    • Organizer
      日本薬学会第141年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] TおよびB細胞のナルディライジンによる抗体産生調節機構の解明2021

    • Author(s)
      茶谷元晴, 茶谷元晴, 藤井貴之, 藤堂景史, 大野美紀子, 西清人, 平田多佳子, 安藤朗, 西英一郎
    • Organizer
      第26回日本病態プロテアーゼ学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肝細胞のナルディライジンは褐色脂肪組織の熱産生を制御する2021

    • Author(s)
      西清人, 岩崎広高, 松田真太郎, 松田真太郎, 大野美紀子, 西英一郎
    • Organizer
      第53回日本動脈硬化学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Metalloprotease nardilysin controls heart rate through the transcriptional regulation of ion channels critical for sinus automaticity2021

    • Author(s)
      Ohno M, Matsuura H, Makiyama T, Nishi K, Iwasaki T, Matsuda S, Kita T, Kimura T, and Nishi E.
    • Organizer
      第31回日本循環薬理学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 分岐鎖アミノ酸代謝産物によるピルビン酸代謝制御機構の解明2021

    • Author(s)
      西 清人、西 英一郎、Rong Tian
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脂肪細胞のNardilysinは細胞における酸素需要および低酸素誘導因子(HIF1-α)シグナルを介してインスリン感受性を制御する2021

    • Author(s)
      松田真太郎、岩﨑広高、西 清人、大野美紀子、西英一郎
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ナルディライジンによる核内受容体ROR/REV-ERB活性調節機構の解明2021

    • Author(s)
      平岡義範、古市真唯、村瀬満政、久米典昭、吉種光、深田吉孝、池田正明、西英一郎
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Nardilysin is a Potential Biomarker for the Early Diagnosis of Non-St-Segment Elevation Acute Coronary Syndrome, A Multicenter Prospective Cohort Study, Nardi-ACS Study2021

    • Author(s)
      Ohno M, Shiomi H, Yano M, Aizawa T, Nakano Y, Yamagami S, Kato M, Ohya M, Chen P-M, Nagao K, Ando K, Kadota K, Yokomatsu T, Inada T, Kurokawa M, Morimoto T, Kimura T, Nishi E
    • Organizer
      American Heart Association’s annual Scientific Sessions 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nardilysin controls cardiac sympathetic innervation patterning through regulation of p75 neurotrophin receptor2020

    • Author(s)
      Ohno M, Nishi K, Hiraoka Y, Niizuma S, Matsuda S, Iwasaki H, Kimura K, and Nishi E
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Metalloprotease nardilysin controls heart rate through the transcriptional regulation of ion channels critical for sinus automaticity2020

    • Author(s)
      Ohno M, Matsuura H., Makiyama T., Nishi K., Iwasaki H., Matsuda S., Kita T., Kimura T., and Nishi E.
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Nardilysin in Adipocyte Regulates Adipose Tissue Inflammation and Insulin Sensitivity2020

    • Author(s)
      松田真太郎、西清人、大野美紀子、西英一郎
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Nardilysin in resected tissue may predict a post-operative prognosis of pancreatic cancer2020

    • Author(s)
      Yasukawa D, Miyake T, Tani M, Nishi E
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] ナルディライジンはp75NTRの調節を介して心臓交感神経分布パターンを調節する2020

    • Author(s)
      大野美紀子、西 清人、平岡 義範、新妻 晋一朗、岩崎 広高、松田 真太郎、木村 剛、西 英一郎
    • Organizer
      第30回日本循環薬理学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Nardilysin controls cardiac sympathetic innervation patterning through regulation of p75 neurotrophin receptor.2020

    • Author(s)
      Ohno M, Nishi K, Hiraoka Y, Niizuma S, Matsuda S, Iwasaki H, Kimura K, and Nishi E
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 脂肪細胞のNardilysinは脂肪組織の酸素需要およびインスリン感受性を制御する2020

    • Author(s)
      松田真太郎、岩﨑広高、大野美紀子、西英一郎
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Book] 創薬研究者・アカデミア研究者が知っておくべき最新の免疫学とその応用技術2021

    • Author(s)
      執筆者:101名、技術情報協会
    • Total Pages
      598
    • Publisher
      技術情報協会
    • ISBN
      9784861048562
    • Related Report
      2021 Annual Research Report
  • [Remarks] 滋賀医科大学 薬理学講座 ホームページ

    • URL

      http://www.shiga-med.ac.jp/pharm/index.html

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Patent(Industrial Property Rights)] 特許2020

    • Inventor(s)
      西 英一郎 他
    • Industrial Property Rights Holder
      西 英一郎 他
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-129627
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2023-01-30  

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