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Beyond Steroids: Toward the Development of Novel Therapies for Autoimmune Diseases.

Research Project

Project/Area Number 22K19428
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) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords自己免疫疾患 / ステロイド / ナルディライジン / ペプチダーゼ、 / ペプチダーゼ
Outline of Research at the Start

我が国では、原因不明で後遺症を残すおそれが少なくない300疾患以上が指定難病に認定されています。指定難病の中には、自己免疫機序を原因とし、ステロイドが唯一無二の治療薬として用いられている疾患が多くあり、長期内服が必要な患者は、その多岐にわたる副作用に苦しめられています。本研究では、ナルディライジンという分子を標的とする治療薬が、ステロイドの代替薬となる可能性を追求します。

Outline of Final Research Achievements

Diseases caused by autoimmune mechanisms include many diseases for which effective treatments are scarce and steroids are the only therapeutic agents. We investigated the potential of nardilysin (NRDC)-targeted therapies as an alternative to steroids, as mouse deficient in NRDC (NRDC-KO) conferred disease resistance in several inflammatory models. In this study, we used T- and B-cell-specific deficient mice and showed that NRDC expressed in lymphocytes may play an important role in the pathogenesis of several autoimmune diseases (autoimmune hepatitis and systemic lupus erythematosus).

Academic Significance and Societal Importance of the Research Achievements

我が国では、原因不明、治療方針が未確定で後遺症を残すおそれが少なくない300以上の疾患を指定難病と認定してます。その中には自己免疫機序を原因とし、ステロイドが唯一の治療薬である疾患が多く含まれていますが、ステロイドの長期内服が必要な患者は、その重篤な副作用に苦しめられています。我々は、ナルディライジン(NRDC)という分子を欠損したマウスを用い研究を行い、この分子を抑制することが新たな自己免疫性疾患治療薬開発につながる可能性を示しました。今後もNRDCを標的とする治療薬がステロイドの代替となる可能性を追求します。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (27 results)

All 2024 2023 2022 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (19 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Null mutation of exocyst complex component 3-like does not affect vascular development in mice2024

    • Author(s)
      Takashima Satsuki、Okamura Eiichi、Ichiyama Yusuke、Nishi Kiyoto、Shimizu Akio、Watanabe Chisato、Muto Masanaga、Matsumoto Shoma、Tsukiyama-Fujii Setsuko、Tsukiyama Tomoyuki、Ogita Hisakazu、Nishi Eiichiro、Ohji Masahito、Sugiyama Fumihiro、Takahashi Satoru、Mizuno Seiya、Mizutani Ken-ichi、Ema Masatsugu
    • Journal Title

      Experimental Animals

      Volume: 73 Issue: 1 Pages: 93-100

    • DOI

      10.1538/expanim.23-0105

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nardilysin determines hematopoietic stem cell fitness by regulating protein synthesis2024

    • Author(s)
      Oshima Shinichiro、Sinha Rahul、Ohno Mikiko、Nishi Kiyoto、Eto Koji、Takaori-Kondo Akifumi、Nishi Eiichiro、Yamamoto Ryo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 693 Pages: 149355-149355

    • DOI

      10.1016/j.bbrc.2023.149355

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Auxiliary roles of nardilysin in the early diagnosis of acute coronary syndrome: a prospective cohort study, the Nardi-ACS study2024

    • Author(s)
      Ohno M, Shiomi H, Baba O, Yano M, Aizawa T, Nakano-Matsumura Y, Yamagami S, Kato M, Ohya M, Chen PM, Nagao K, Ando K, Yokomatsu T, Kadota K, Kouchi I, Inada T, Valentine C, Kitagawa T, Kurokawa M, Ohtsuru S, Morimoto T, Kimura T, Nishi E
    • Journal Title

      Internal and Emergency Medicine

      Volume: 19 Issue: 3 Pages: 649-659

    • DOI

      10.1007/s11739-023-03508-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Subclinical myocardial damage after anthracycline chemotherapy in Japanese patients with breast cancer2024

    • Author(s)
      Nakatsuma Kenji、Ozasa Neiko、Ohno Mikiko、Ishiguro Hiroshi、Minami Manabu、Nishi Eiichiro、Toi Masakazu、Ono Koh、Kimura Takeshi
    • Journal Title

      Journal of Cardiology

      Volume: 0 Issue: 4 Pages: 0-0

    • DOI

      10.1016/j.jjcc.2024.03.005

    • Related Report
      2023 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
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] NRDC in vascular smooth muscle cells controls vascular contraction and blood pressure via the regulation of calcium mobilization2024

    • Author(s)
      Mend Amar Batbaatar, Mikiko Ohno, Takeshi Kinoshita, Kiyoto Nishi, Shinya Ikeda, Eiichiro Nishi
    • Organizer
      第33回日本循環薬理学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] M16メタロエンドペプチダーゼによる洞機能制御機構2024

    • Author(s)
      大野 美紀子, 松浦 博, 西 清人,糀谷 泰彦, 牧山 武,池田 真也, 西 英一郎
    • Organizer
      第33回日本循環薬理学会
    • Related Report
      2023 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2024

    • Author(s)
      西 清人,大野 美紀子,西 英一郎, Rong Tian
    • Organizer
      第33回日本循環薬理学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Role of a multifunctional peptidase nardilysin in homeostasis2023

    • Author(s)
      Nishi E
    • Organizer
      12th General Meeting of the International Proteolysis Society
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Nardilysin in hepatocyte regulates diet-induced thermogenesis via the modulation of brown adipose tissue activity2023

    • Author(s)
      Kiyoto Nishi, Hirotaka Iwasaki, Mikiko Ohno and Eiichiro Nishi
    • Organizer
      12th General Meeting of the International Proteolysis Society
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NRDC in vascular smooth muscle cells regulates vascular contraction and blood pressure2023

    • Author(s)
      Mend Amar Batbaatar, Mikiko Ohno, Takeshi Kinoshita, Kiyoto Nishi, Eiichiro Nishi
    • Organizer
      第28回日本病態プロテアーゼ学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ナルディライジンに着目した自己免疫性肝炎の病態解明2023

    • Author(s)
      吉田 晋也,西 清人,里岡 大樹,大野 美紀子,平田 多佳子,安藤 朗,西 英一郎
    • Organizer
      第28回日本病態プロテアーゼ学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ナルディライジンの酵素活性阻害薬のスクリーニング2023

    • Author(s)
      佐野芳珠季,西清人,大野美紀子,西英一郎
    • Organizer
      第28回日本病態プロテアーゼ学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ナルディライジンによる循環動態制御機構2023

    • Author(s)
      大野 美紀子,西 清人,西 英一郎
    • Organizer
      第28回日本病態プロテアーゼ学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Enzymatic activity of nardilysin plays significant roles in the regulation of central nervous system activity2023

    • Author(s)
      Mikiko Ohno, Shigeyuki Esumi, Tetsuya Obayashi, Takayuki Fujii, Kiyoto Nishi, Shinya Ikeda, Eiichiro Nishi
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Nardilysin in hepatocyte regulates brown adipose tissue activity2023

    • Author(s)
      Kiyoto Nishi、Hirotaka Iwasaki、Mikiko Ohno、Eiichiro Nishi
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ナルディライジンは制御性T細胞を介して自己免疫性肝炎に関与する2023

    • Author(s)
      吉田 晋也、里岡 大樹、西 清人、大野 美紀子、平田 多佳子、安藤 朗、西 英一郎
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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
      2023 Annual Research Report 2022 Research-status Report

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Published: 2022-07-05   Modified: 2025-01-30  

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