Pathogenic action of CADM1 shedding in neurodegeneration
Project/Area Number |
16K08723
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
|
Research Institution | Kindai University |
Principal Investigator |
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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.
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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。
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Report
(4 results)
Research Products
(4 results)