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Investigation of the mechanisms by which Multifaceted Homeostasis is maintained by Nardilysin

Research Project

Project/Area Number 20H03449
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionShiga University of Medical Science

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 大野 美紀子  滋賀医科大学, 医学部, 准教授 (10583198)
岩崎 広高  滋賀医科大学, 医学部, 助教 (40781589)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords恒常性 / エネルギー代謝 / 抗体産生 / ペプチダーゼ / ナルディライジン
Outline of Research at the Start

ナルディライジン(NRDC)欠損マウスは、低体温、低インスリン血症、徐脈などを呈したが、運動量、酸素消費量は上昇しており、寿命短縮は認めなかったことから、野生型マウスとは異なるセットポイントで恒常性、健康を維持しているマウスと考えられた。本研究では、エネルギー代謝および免疫系に焦点をあてて、NRDCが恒常性維持において果たす役割を明らかにする。さらにペプチダーゼであるNRDCの基質タンパク質同定を試み、ペプチダーゼ活性の役割を解明する。

Outline of Final Research Achievements

Homeostasis is the tendency for the body's internal environment to remain within a certain range. Body temperature is maintained at a constant level regardless of the outside temperature, and even when pathogens infect the body, the immune system attempts to eliminate them and restore homeostasis. Nardilysin (NRDC) is a protease that is deeply involved in the maintenance of various homeostasis. In this study, we found that NRDC in the liver play an important role in energy metabolism, such as the maintenance of body temperature, while NRDC in lymphocytes play an important role in the maintenance of the immune mechanism. NRDC may be involved in the phenomenon in which the body becomes warm after eating.

Academic Significance and Societal Importance of the Research Achievements

本研究およびこれまでの研究は、異なる臓器や細胞に発現するNRDCが、様々な恒常性維持に重要であることを示しました。本研究で示したエネルギー代謝におけるNRDCの役割は、肥満や糖尿病の理解や治療に役立つ可能性があります。また免疫におけるNRDCの役割は、免疫力が自身を攻撃してしまうことで生じるアレルギーやリウマチなどの病気の理解や治療に役立つ可能性があります。いわゆる難病とよばれる治療法の乏しい病気には、自己免疫が原因になっているものが多いので、本研究の発展が新たな治療法開発につながることが期待されます。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (41 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (23 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Technion-Israel Institute of Technology(イスラエル)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Technion-Israel Institute of Technology(イスラエル)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer2023

    • Author(s)
      Li SY, Yoshida Y, Kubota M, 他10名, Ohno M, Nishi E, Kitamura K, Kamitsukasa I, Takizawa H, Sata M, Yamagishi K, Iso H, Sawada N, Tsugane S, Iwase K, Shimada H, Iwadate Y, Hiwasa T.
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 10 Pages: 1-19

    • DOI

      10.3389/fcvm.2023.1042272

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunohistochemical and clinicopathological study regarding nardilysin on extramammary Paget's disease2023

    • Author(s)
      Yamaguchi Akihiko、Takahashi Toshifumi、Kato Takeshi、Tanaka Toshihiro、Nishi Eiichiro、Fujimoto Noriki
    • Journal Title

      Archives of Dermatological Research

      Volume: 10 Issue: 7 Pages: 1-9

    • DOI

      10.1007/s00403-023-02579-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ketone bodies: A double‐edged sword for mammalian life span2023

    • Author(s)
      Tomita Issei、Tsuruta Hiroaki、Yasuda‐Yamahara Mako、Yamahara Kosuke、Kuwagata Shogo、Tanaka‐Sasaki Yuki、Chin‐Kanasaki Masami、Fujita Yukihiro、Nishi Eiichiro、Katagiri Hideki、Maegawa Hiroshi、Kume Shinji
    • Journal Title

      Aging Cell

      Volume: in press Issue: 6 Pages: 1-5

    • DOI

      10.1111/acel.13833

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

      Sci Rep.

      Volume: 12 Issue: 1 Pages: 3449-3449

    • DOI

      10.1038/s41598-022-07379-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

      Biological and Pharmaceutical Bulletin

      Volume: 44 Issue: 3 Pages: 363-371

    • DOI

      10.1248/bpb.b20-00722

    • NAID

      130007993442

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2021-03-01
    • Related Report
      2020 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 Issue: 1 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 Issue: 1 Pages: 1161-1161

    • DOI

      10.1038/s41598-020-80742-y

    • NAID

      120006953800

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Annual Research 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

      Int J Mol Med

      Volume: 46 Pages: 1274-1288

    • DOI

      10.3892/ijmm.2020.4690

    • Related Report
      2020 Annual Research 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 Issue: 8 Pages: e04661-e04661

    • DOI

      10.1016/j.heliyon.2020.e04661

    • Related Report
      2020 Annual Research 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 Sci

      Volume: 111 Issue: 12 Pages: 4453-4464

    • DOI

      10.1111/cas.14652

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] タコツボ症候群における多機能プロテアーゼの役割2023

    • Author(s)
      大野 美紀子、西 清人、西 英一郎
    • Organizer
      第32回日本循環薬理学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 分岐鎖アミノ酸代謝産物はピルビン酸輸送を介して糖新生を抑制する2022

    • Author(s)
      西 清人、西 英一郎、Rong Tian
    • Organizer
      第24回・第25回日本病態栄養学会年次学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] The regulatory roles of branched-chain amino acid metabolites in pyruvate metabolism2022

    • Author(s)
      Kiyoto Nishi、Eiichiro Nishi、Rong Tian
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ナルディライジンによる抗体産生調節機構の解明およびDSS腸炎モデルでの検討2022

    • Author(s)
      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, 西 英一郎, 安藤 朗
    • Organizer
      第59回日本消化器免疫学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ナルディライジン酵素活性の生体内における意義2022

    • Author(s)
      大野 美紀子, 松浦 博, 牧山 武, 糀谷 泰彦, 西 清人, 西 英一郎
    • Organizer
      第27回日本病態プロテアーゼ学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 多機能プロテアーゼによる洞機能制御機構2022

    • Author(s)
      大野 美紀子, 松浦 博, 牧山 武, 糀谷 泰彦, 西 清人, 西 英一郎
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Nardilysin in hepatocyte regulates diet-induced thermogenesis via the modulation of brown adipose tissue activity2022

    • Author(s)
      Kiyoto Nishi、Hirotaka Iwasaki、Mikiko Ohno、Shintaro Matsuda、Eiichiro Nishi
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2022 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] 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 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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research 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
      2022 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 Annual Research 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 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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