| Project/Area Number |
18K16273
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Chiba University |
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Principal Investigator |
OITA Satoru 千葉大学, 医学部附属病院, 医員 (90813543)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | Ncx / Ecel1 / 腸管神経培養 / アポトーシス / primary culture / apoptosis / 腸管神経 / ヒルシュスプルング類縁疾患 |
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| Outline of Final Research Achievements |
In this study, we clarified the relationship between Ncx and Ecel1 and the enteric nervous system. Ecel1 was identified as a target molecule of the transcription factor Ncx by microarray analysis. It was shown that Ecel1 was expressed in the enteric neuron and the expression was increased in Ncx-/-mice. Knockdown of NCX increased the expression of ECEL1 in SH-SY5Y neuroblastoma cells. In addition, reporter gene analysis revealed that Ncx acts on the promoter region of Ecel1 and negatively regulates the expression of Ecel1. The number of cleaved caspase3-positive neurons was decreased in Ncx-/-mice compared to that of wild type mice in primary enteric neuron culture. That indicates the inhibition of neuronal apoptosis may lead to hyperplasia of enteric nervous system in Ncx-/-mice.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、NcxをノックアウトすることでEcel1が過剰発現し、正常な腸管神経細胞死が妨げられ、腸管神経過形成を引き起こす可能性が考えられた。また、Ncx-/-腸管神経初代培養ではシナプス形成数が減少していることが示されたことから、異常なシナプス形成がNcx-/-マウスに腸管機能不全を起こしている可能性が考えられた。これにより、腸管神経の発生に新たな知見を加えるとともに、ヒルシュスプルング病類縁疾患の一つである腸管神経形成異常症を含む、原因不明の腸管蠕動不全を起こす疾患の病因究明や新たな診断ツールとして役立つ可能性がある。
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