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Mechanistic insights of the pathogenesis of alopecia using a novel vitamin D-dependent richets mouse model

Research Project

Project/Area Number 18K19518
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionThe University of Tokushima

Principal Investigator

SAWATSUBASHI Shun  徳島大学, 先端酵素学研究所, 特任准教授 (70535103)

Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsビタミンD / ビタミンD受容体 / 転写 / くる病 / 脱毛 / ゲノム編集 / 毛包 / 毛周期 / 核内受容体 / 退縮期 / ビタミンD依存性くる病 / 点変異
Outline of Final Research Achievements

The hair follicle is a dynamically regenerating organ, and the hair cycle is an important model for regeneration research. In this study, we focused on the pathogenesis of hair loss in a vitamin D-dependent rickets model mouse, and aimed to clarify the regulatory mechanism of the catagen, which has not yet been elucidated.
As a result, we established a novel mouse model of rickets that mimics point mutations in human disease. Furthermore, we succeeded in establishing 10 strains of the VDR mutations using genome editing, and investigated the pathophisiology. Interestingly, each point-mutated VDR showed differences in the interacting proteins that reduced their binding ability. This is an important result to reconsider the conventional disease mechanism, in which the loss of interaction with RXR, a heterodimer of VDR, has been considered as the main cause.

Academic Significance and Societal Importance of the Research Achievements

毛を生み出す毛包は、成長期・退縮期・休止期を周期的に繰り返す動的に維持された器官であり、幹細胞研究に用いられてきた。従来は発毛の観点で、どのように成長期が制御されるか、に主眼をおいた研究が展開されており、退縮期の制御に焦点を当てた研究は驚くほど少ない。本研究は、将来的な脱毛の治療法の開発を指向し、指定難病であるビタミンD依存性くる病でみられる禿頭や、加齢とともに生じる脱毛の原因を解明することを試みた。結果として、毛産生細胞が不要となったステージで、正しく消去される機構の重要性が見出され、その破綻の結果として残存する『居残り細胞』が病態を引き起こすという新たなモデルを創出することができた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2020 2019 2018 Other

All Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (7 results) Book (2 results) Remarks (4 results)

  • [Journal Article] How do we sense phosphate to regulate serum phosphate level?2020

    • Author(s)
      Seiji Fukumoto, Yuichi Takashi, Maria Tsoumpra, Shun Sawatsubashi, Toshio Matsumoto
    • Journal Title

      Journal of Bone and Mineral Metabolism

      Volume: 38 Issue: 1 Pages: 1-6

    • DOI

      10.1007/s00774-019-01066-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dystrobrevin alpha gene is a direct target of the vitamin D receptor in muscle2020

    • Author(s)
      Tsoumpra Maria K、Sawatsubashi Shun、Imamura Michihiro、Fukumoto Seiji、Takeda Shin’ichi、Matsumoto Toshio、Aoki Yoshitsugu
    • Journal Title

      Journal of Molecular Endocrinology

      Volume: 64 Issue: 3 Pages: 195-208

    • DOI

      10.1530/jme-19-0229

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation2019

    • Author(s)
      Takashi Y, Kosako H, Sawatsubashi S, Kinoshita Y, Ito N, Tsoumpra MK, Nangaku M, Abe M, Matsuhisa M, Kato S, Matsumoto T, Fukumoto S
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 116 Issue: 23 Pages: 11418-11427

    • DOI

      10.1073/pnas.1815166116

    • NAID

      120006715989

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Function of the Vitamin D Receptor and a Possible Role of Enhancer RNA in Epigenomic Regulation of Target Genes: Implications for Bone Metabolism2019

    • Author(s)
      Sawatsubashi Shun、Nishimura Koichi、Mori Jinichi、Kouzmenko Alexander、Kato Shigeaki
    • Journal Title

      Journal of Bone Metabolism

      Volume: 26 Issue: 1 Pages: 3-12

    • DOI

      10.11005/jbm.2019.26.1.3

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protocol for CRISPR/Cas9-based knock-in using the VIKING method2019

    • Author(s)
      Joko Yudai、Sugano Shigeo S.、Fukumoto Seiji、Matsumoto Toshio、Sawatsubashi Shun
    • Journal Title

      Protocol Exchange

      Volume: 01-24

    • DOI

      10.1038/protex.2019.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 栄養情報が調節するグルココルチコイド受容体の転写制御機構の解析2020

    • Author(s)
      沢津橋俊、松本俊夫、福本誠二
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 表皮・毛包の恒常性におけるビタミンD受容体の機能解析2020

    • Author(s)
      沢津橋俊、松本俊夫、福本誠二
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 骨特異的FGFR1欠失マウスを用いたリン感知分子としてのFGFR1の解析2020

    • Author(s)
      高士祐一、沢津橋俊、遠藤逸郎、安倍正博、松久宗英、田邉真紀人、川浪大治、松本俊夫、福本誠二
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ゲノム編集を利用したくる病点変異導入ビタミンD受容体の機能解析2019

    • Author(s)
      沢津橋俊、横山敦、上甲裕大、松本俊夫、福本誠二
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 栄養情報が調節するグルココルチコイド受容体の転写制御機構の解明2019

    • Author(s)
      沢津橋俊、松本俊夫、福本誠二
    • Organizer
      第37回内分泌代謝学サマーセミナー
    • Related Report
      2019 Research-status Report
  • [Presentation] 表皮・毛包の恒常性におけるビタミンD受容体の機能解析2018

    • Author(s)
      沢津橋俊、上甲裕大、松本俊夫、福本誠二
    • Organizer
      第36回内分泌代謝学サマーセミナー
    • Related Report
      2018 Research-status Report
  • [Presentation] VIKING法によるノックアウト/ノックイン細胞を用いた比較プロテオーム解析によるビタミンD受容体複合体の探索2018

    • Author(s)
      沢津橋俊、横山敦、上甲裕大、菅野茂夫、松本俊夫、福本誠二
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Book] Encyclopedia of Bone Biology 1st Edition Mechanisms of Osteoprotective Actions of Estrogens2020

    • Author(s)
      Shigeaki Kato, Shun Sawatsubashi, Atsushi Yokoyama, Takashi Nakamura, Alexander Kouzmenko
    • Total Pages
      2374
    • Publisher
      Academic Press
    • ISBN
      9780128140819
    • Related Report
      2020 Annual Research Report
  • [Book] 実験医学2019年7月号 培養細胞における簡便なノックインを可能とするゲノム編集法:VIKING法2019

    • Author(s)
      沢津橋俊, 上甲裕大, 菅野茂夫
    • Total Pages
      145
    • Publisher
      羊土社
    • ISBN
      9784758125215
    • Related Report
      2019 Research-status Report
  • [Remarks] 分子内分泌学研究分野 基幹研究部門 ホルモンによる生体機能調節機序の解明

    • URL

      http://www.iams.tokushima-u.ac.jp/lab/fukumoto/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 徳島大学藤井節郎記念医科学センター 分子内分泌学研究分野

    • URL

      https://www.fujii.tokushima-u.ac.jp/nuclearreceptor/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 徳島大学 / 教育研究者総覧

    • URL

      http://pub2.db.tokushima-u.ac.jp/ERD/person/278225/work-ja.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 徳島大学藤井節郎記念医科学センター分子内分泌学研究分野

    • URL

      http://www.fujii.tokushima-u.ac.jp/nuclearreceptor/

    • Related Report
      2019 Research-status Report

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Published: 2018-07-25   Modified: 2022-01-27  

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