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Pathogenic action of CADM1 shedding in neurodegeneration

Research Project

Project/Area Number 16K08723
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionKindai University

Principal Investigator

YONESHIGE Azusa  近畿大学, 医学部, 助教 (70586750)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経変性 / 接着分子 / 腸管神経系 / 緑内障 / 病的内圧上昇 / 細胞接着分子 / 静的圧力 / 細胞死 / 細胞傷害
Outline of Final Research Achievements

CADM1 is an adhesion molecule expressed abundantly in neurons and epithelial cells. We have revealed that ectodomain shedding of CADM1 is occurred in emphysema, interstitial pneumonia and diabetes and that CADM1 shedding leads to cell apoptosis. In this study, to elucidate pathogenic action of CADM1 shedding in neurodegeneration, we investigated the correlation between enteric nerve degeneration and CADM1 shedding in dilated colon with tumor-induced stenosis. CADM1 shedding rate was increased proportionately with colon dilation in association with decrease of ganglion cells and neurites. Using two-chamber cell culture system enable to loading modest static pressure to the cultured cells, we showed that increasing pressure induced CADM1 shedding and the decreases of neurite density and thickness. Exogenous expression of CADM1 shedding product resulted in neurites loss, suggesting its involvement in neurodegeneration.

Academic Significance and Societal Importance of the Research Achievements

筆者らの研究グループはこれまでに肺気腫や間質性肺炎の肺、2型糖尿病の膵臓におけるCADM1 sheddingの亢進と各CADM1発現細胞の変性/細胞死との関わりを研究してきた。本研究は神経変性疾患においても同様の現象が起こっていることを示し、細胞接着分子のsheddingが慢性疾患の病態形成において普遍的な現象である可能性を示唆した点において意義深い。また新規に開発した培養装置を用いて、病的内圧上昇と神経変性との直接的な関連を証明し、緑内障など、より社会的要求性の高い疾患研究への応用可能性を示した。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2018 2016

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Expression of cell adhesion molecule 1 in gastric neck and base glandular cells: possible involvement in peritoneal dissemination of signet ring cells.2018

    • Author(s)
      Kimura R, Yoneshige A, Hagiyama M, Otani T, Inoue T, Shiraishi N, Yanagihara K, Wakayama T, Ito A.
    • Journal Title

      Life Sci

      Volume: 213 Pages: 206-213

    • DOI

      10.1016/j.lfs.2018.10.017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early Gene Expression Profile in Retinal Ganglion Cell Layer After Optic Nerve Crush in Mice.2018

    • Author(s)
      Ueno S, Yoneshige A, Koriyama Y, Hagiyama M, Shimomura Y, Ito A.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 59 Issue: 1 Pages: 370-380

    • DOI

      10.1167/iovs.17-22438

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modest static pressure can cause enteric nerve degeneration through ectodomain shedding of cell adhesion molecule 1.2016

    • Author(s)
      Yoneshige A, Hagiyama M, Inoue T, Tanaka T, Ri A, Ito A
    • Journal Title

      Mol Neurobiol

      Volume: - Issue: 8 Pages: 1-1

    • DOI

      10.1007/s12035-016-0166-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Enteric nerve degeneration in the colon dilated due to the luminal stenosis by cancer: involvement of CADM1/TSLC12016

    • Author(s)
      Hagiyama M, Yoneshige A, Ito A.
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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