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Development of a novel treatment for Sjogren's syndrome on the basis of the regulation of molecules related to the syndrome

Research Project

Project/Area Number 17K11842
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

AZUMA Masayuki  徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (20144983)

Co-Investigator(Kenkyū-buntansha) 青田 桂子  徳島大学, 病院, 准教授 (70437391)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsシェーグレン症候群 / 腺房細胞 / 導管細胞 / アクアポリン5 / ケモカイン / サイトカイン / 転写因子NF-kB / 唾液腺 / ケモカインレセプター
Outline of Final Research Achievements

We examined the therapeutic effect of Bortezomib, an NF-kB-inhibitory drug, on the destruction of acinar structure of SjS model mouse. As a result, Bortezomib was shown to improve the destruction of acinar structure by suppressing the NF-kB activity of acinar cells.
We examined the effects of HDAC inhibitors on the expression of AQP5 in cultured acinar cells. As a consequence, increase of the expression of AQP5 mRNA was observed by the treatment of acinar cells with HDAC inhibitors. In addition, it was shown that HDAC inhibitors induce the expression of AQP5 in acinar cells by inhibiting the deacetylation of histone H4 in promoter regions.

Academic Significance and Societal Importance of the Research Achievements

本研究はSjSの発症に関与する分子群を発現制御することにより、多段階的・多重的な治療法を構築するところにある。すなわち、唾液腺組織へのリンパ球浸潤を阻止するためCXCL10分子を標的とする治療法の構築、また腺房構造破壊に関与する転写因子NF-kBを標的とした治療法の構築、さらに腺房細胞における水分泌機能向上のために、水輸送膜蛋白であるAQP5の発現を誘導する治療法の構築である。本治療法は患者が置かれているあらゆる病期・病態に対応できるシステムである。よって本研究成果は、患者にとって最適な治療法の選択と治療効果の実質的実現につながることから学術的意義や社会的意義は非常に大きいものと考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report

Research Products

(21 results)

All 2020 2019 2018 2017

All Journal Article Presentation Book

  • [Journal Article] PLAG1 enhances the stemless profiles of acing cells in normal human salivary glands in a cell type-specific manner.2020

    • Author(s)
      Goto Y, Ibi M, Tanaka J, Yasuhara R, Aota K, Azuma M, Fukuda T, Mishima K, Irie T.
    • Journal Title

      Journal of Oral Biosciences

      Volume: 55 Pages: 1-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MMP-9 inhibition suppresses interferon-g-induced CXCL10 production in human salivary gland cells.2019

    • Author(s)
      Aota K, Ono S, Yamanoi T, Kani K, Momota Y, Azuma M.
    • Journal Title

      Inflammation

      Volume: 42 Pages: 2148-2158

    • DOI

      10.1007/s10753-019-01079-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sox9 regulates the luminal stem/progenitor cell properties of salivary glands.2019

    • Author(s)
      Tanaka Junichi、Mabuchi Yo、Hata Kenji、Yasuhara Rika、Takamatsu Koki、Kujiraoka Satoko、Yukimori Akane、Takakura Ikuko、Sumimoto Hidetoshi、Fukada Toshiyuki、Azuma Masayuki、Akiyama Haruhiko、Nishimura Riko、Shimane Toshikazu、Mishima Kenji
    • Journal Title

      Exp Cell Res

      Volume: 382 Pages: 111449-111449

    • DOI

      10.1016/j.yexcr.2019.05.030

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Management of tooth extraction in a patient with ELANE gene mutation-induced cyclic neutropenia: A case report.2019

    • Author(s)
      Keiko Aota, Koichi Kani, Tomoko Yamanoi, Yukihiko Momota, Masami Ninomiya, Hiromichi Yumoto, Masayumi Azuma
    • Journal Title

      Medicine (Baltimore)

      Volume: 98 Pages: 1-8

    • DOI

      10.1097/md.0000000000017372

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cepharanthine inhibits IFN-g-induced CXCL10 by suppressing the JAK2/STAT1 signal pathway in human salivary gland ductal cells2018

    • Author(s)
      Aota Keiko、Yamanoi Tomoko、Kani Koichi、Azuma Masayuki
    • Journal Title

      Inflammation

      Volume: 41 Pages: 50-58

    • DOI

      10.1007/s10753-017-0662-x

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distinct regulation of CXCL10 production by cytokines in human salivary gland ductal and acing cells2018

    • Author(s)
      Aota K, Kani K, Yamanoi T, Nakashiro KI, Ishimaru N, Azuma M.
    • Journal Title

      Inflammation

      Volume: - Pages: 1172-1181

    • DOI

      10.1007/s10753-018-0764-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inverse correlation between the number of CXCR3+ macrophages and the severity of inflammatory lesion in Sjogren’s syndrome salivary glands: A pilot study.2018

    • Author(s)
      Aota K, Yamanoi T, Kani K, Nakashiro K, Ishimaru N, Azuma M.
    • Journal Title

      J Oral Pathol Med

      Volume: 47 Pages: 710-718

    • DOI

      10.1111/jop.12756

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] CCL22-producting resident macrophages enhance T cell response in Sjogren's syndrome2018

    • Author(s)
      Ushio A, Arakaki R, Otsuka K, Yamada A, Tsunematsu T, Kudo Y, Aota K, Azuma M, Ishimaru N
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 1-15

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Treatment with the biscoclaurine alkaloid cepharanthine significantly increases salivary secretion in primary Sjogren syndrome patients.2017

    • Author(s)
      Tomato Yamanoi, Keiko Aota, Yukihiro Momota, Masayuki Azuma
    • Journal Title

      Journal of Oral Health and Biosciences

      Volume: 29 Pages: 39-48

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] シェーグレン症候群の病態形成におけるCXCL10-CXCR3の役割2019

    • Author(s)
      青田桂子、山ノ井朋子、可児耕一、石丸直澄、東 雅之
    • Organizer
      第73回日本口腔科学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 唾液腺導管細胞のIFN-g誘導性CXCL10過剰発現におけるMMP-9の役割2019

    • Author(s)
      青田桂子、山ノ井朋子、可児耕一、東 雅之
    • Organizer
      第56回日本口腔組織培養学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト唾液腺細胞株の樹立とその応用ーシェーグレン症候群の発症機序の解明と治療ー2018

    • Author(s)
      青田桂子
    • Organizer
      第36回日本ヒト細胞学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 唾液腺細胞におけるCXCL10発現機構の解析2018

    • Author(s)
      青田桂子、山ノ井朋子、可児耕一、桃田幸弘、東 雅之
    • Organizer
      第72回日本口腔科学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] DocetaxelとG-tocotrienolの時差投与による口腔癌細胞株に対する抗腫瘍効果の検討2018

    • Author(s)
      可児耕一、桃田幸弘、高野栄之、青田桂子、東 雅之
    • Organizer
      第63回日本口腔外科学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 口腔癌移植ヌードマウス腫瘍に対するdocetaxel-g-tocotrienol併用療法による抗腫瘍効果の検討2018

    • Author(s)
      可児耕一、桃田幸弘、高野栄之、青田桂子、山ノ井朋子、東 雅之
    • Organizer
      第17回中四国口腔癌研究会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 三剤併用が奏功した一次性舌痛症の3例ー口腔領域の難治性疼痛への対応ー2017

    • Author(s)
      桃田幸弘、高野栄之、可児耕一、松本文博、青田桂子、山ノ井朋子、高瀬奈緒、宮本由貴、小野信二、東 雅之
    • Organizer
      第62回日本口腔外科学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] A case series of xerostomia treated with kakapo medicines: Assessment of health-related quality of life based on the Japanese version of the short form-8 health survey.2017

    • Author(s)
      Momota Y, Takano H, Kani K, Matsumoto Y, Aota K, Yamanoi T, Takase N, Miyamoto Y, Ono S, Azuma M
    • Organizer
      23rd International Conference on Oral and Maxillofacial Surgery
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 口腔機能管理を行った重症多形滲出性紅斑の2例2017

    • Author(s)
      高野栄之、桃田幸弘、小野信二、可児耕一、松本文博、青田桂子、金川裕子、東 雅之
    • Organizer
      第14回日本口腔ケア学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 五苓散と加工附子末製剤の併用が奏功した三叉神経痛の1例2017

    • Author(s)
      桃田幸弘、高野栄之、可児耕一、東 雅之
    • Organizer
      第71回日本口腔科学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 混合歯列期にBP製剤が投与された骨形成不全症の1例2017

    • Author(s)
      高野栄之、桃田幸弘、可児耕一、椎野 滋、東 雅之
    • Organizer
      第27回日本口腔内科学会
    • Related Report
      2017 Research-status Report
  • [Book] 臨床免疫・アレルギー科2017

    • Author(s)
      東 雅之
    • Total Pages
      121
    • Publisher
      科学評論社
    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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