| Project/Area Number |
17K11651
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
NEZU Akihiro 北海道医療大学, 歯学部, 准教授 (00305913)
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| Co-Investigator(Kenkyū-buntansha) |
森田 貴雄 日本歯科大学, 新潟生命歯学部, 教授 (20326549)
谷村 明彦 北海道医療大学, 歯学部, 教授 (70217149)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 代償性肥大 / 唾液分泌機能亢進 / In vivo Ca2+ imaging / 遺伝子発現 / Ca2+ イメージング / 誘導シグナル / 唾液分泌 / 分泌機能亢進 / 細胞内Ca2+応答 / 唾液腺 / Ca2+応答 / 代償性肥大機序 / 生体イメージング / 網羅的遺伝子発現解析 |
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| Outline of Final Research Achievements |
Dysfunction of unilateral salivary glands causes compensatory hypertrophy of the contralateral gland. We developed a method for real-time imaging of Ca2+ responses with simultaneous monitoring of salivary secretion in vivo, and found that ligation of main excretory duct (MED) of unilateral submandibular gland (SMG) induced compensatory hypertrophy in association with enhancement of low doses of acetylcholine-induced salivation and Ca2+ response. To clarify the mechanism of the compensatory hyperfunctional SMG, we examined changes in gene expression in SMG which are induced by MED ligation. Using the comprehensive analyses of mRNA expression, we found that 6 genes were significantly changed in contralateral SMG. We then examined immunohistochemical analysis using anti-PCNA antibodies, and found that the number of PCNA positive cells was increased in acinar cells in 3 days. These results suggest that disorder of unilateral SMG causes acinar cell proliferation at a relatively early stage.
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| Academic Significance and Societal Importance of the Research Achievements |
唾液腺の代償性肥大による分泌増加のしくみは単に組織肥大により起こると考えられていた。本研究によって、腺肥大だけでなく分泌刺激に対する唾液腺細胞の感受性の亢進が起こっていることが初めて明らかになった。そこで機能亢進を誘導するシグナルの分子基盤を明らかにするため、網羅的遺伝子解析を行ったところ、肥大腺で変化する6つに遺伝子の同定に成功した。これらをマーカーとし誘導シグナルを調べたところ、副交感神経からのアセチルコリンだけでなく、他の因子が関わることが明らかとなった。本研究成果を基に薬物投与や標的遺伝子の導入によって機能亢進を人為的に誘導できれば、新たな口腔乾燥症治療法の創生につながると期待できる。
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