Elucidation of the mechanism to improve the cleft palate phenotype with the molecular target drug
| Project/Area Number |
24592788
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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 |
Morphological basic dentistry
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| Research Institution | Asahi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
INTO Takeshi 朝日大学, 歯学部, 講師 (10360918)
TAKAGI Shuta 朝日大学, 歯学部, 元助教 (10711351)
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| Research Collaborator |
SUGIYAMA Akiko 朝日大学, 歯学部, 助教 (90304534)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 口蓋裂 / TGFβ3ノックアウトマウス / 分子標的治療薬 / エピジェネティクス / シグナル伝達系 / 口蓋裂表現型 / 上皮成長因子阻害剤 / DNAメチル化酵素阻害剤 / TGFβ3 ノックアウトマウス / TGFβ3 / 上皮成長因子受容体 / 口蓋裂軽症化作用 / EGFR阻害剤 / ゲフィチニブ / 口蓋突起内側縁上皮細胞 / 上皮ー間葉分化転換 |
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| Outline of Final Research Achievements |
Even if the mice as well as humans carry the same gene mutation, the phenotype differs dependently on the genetic background, but its cause remained enigmatic. This study showed that the phenotype of the genetically induced palatal cleft is dependent on epigenetic modifiers, such as the balance in the expression level of IGF2R and various activated signaling molecules, by using two different strains of TGFβ3 knockout mice. Furthermore, we demonstrated for the first time that administration of molecular target drugs against DNA methyltransferase and epidermal growth factor receptor can improve the severity of the palatal cleft via the elevated expression of IGF2R and the reduced expression of phospho-Erk1/2, respectively. These findings provide insight into new strategies of preventive pharmacological fetal therapy in addition to postnatal surgery against human palatal cleft, to improve the severity of the fetal phenotype of pregnant woman with gene mutation of causing palatal cleft.
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Report
(4 results)
Research Products
(5 results)
