Etiology of cleft palate as multifactorial inheritance disease
| Project/Area Number |
17K19754
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Oral Science and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
黒坂 寛 大阪大学, 歯学部附属病院, 講師 (20509369)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
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| Keywords | Stat3 / Tgfb3 / 口蓋裂 / 癒合 / 口蓋上皮 / 葉酸 / レスキュー / Socs3 / 発生・分化 / 環境因子 / 多因子遺伝子疾患 |
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| Outline of Final Research Achievements |
It is established that Tgfb3 is important in the palatal fusion. The resent study demonstrated that Stat3 phosphorylation regulated the Tgfb3 mRNA expression at the fusion palatal epithelium and was consequently involved in the epithelial fusion. Furthermore, Socs3, an inhibitor of Stat3, regulatded the region of Stat3 phosphorylation in palatogesis. On the other hand, maternal folic acid supplementation has been shown to be as an effective intervention for reducing the
risk of non-syndromic cleft palate. The present study showed that the anterior cleft palate in Cbfb mutants was rescued by pharmaceutical application of folic acid that activates suppressed Stat3 phosphorylation and Tgfb3 expression in vitro. Together, the rescue of the mutant cleft palate using folic acid may elucidate potential therapeutic targets by Stat3 modification for the prevention and pharmaceutical intervention of cleft palate.
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| Academic Significance and Societal Importance of the Research Achievements |
口蓋裂の原因遺伝子は遺伝子改変動物の解析から多数の遺伝子が同定されている。それにも関わらず、口蓋裂が多因子遺伝子疾患であることを説明する分子機構は解明されていない。本研究によってStat3-Tgfb3シグナルが口蓋の癒合に関与することを明らかにした。このシグナルは、様々な分子経路や環境要因によって活性化される可能性があるため、口蓋裂が多因子遺伝子疾患である分子機序に関与していると示唆される。
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Report
(3 results)
Research Products
(2 results)
