Invention of new diffrentiation-inducing therapy of ENS development in Hirschsprung's disease
| Project/Area Number |
17K11521
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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 |
Pediatric surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
Tanaka Nana 順天堂大学, 医学部, 准教授 (50530656)
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| Co-Investigator(Kenkyū-buntansha) |
浦尾 正彦 順天堂大学, 医学部, 教授 (00213504)
宮原 克 順天堂大学, 医学(系)研究科(研究院), 技術員 (00420844)
藤原 なほ 順天堂大学, 医学部, 非常勤講師 (20589543)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ヒルシュスプルング病 / 腸管神経系 / 腸管神経堤細胞 / 細胞外マトリックス / ラミニン / インテグリン / 微小管 |
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| Outline of Final Research Achievements |
We demonstrated that laminin-1 does not have a positive effect on ENCC migration in HD mice, in contrast to the phenomenon seen in normal mice. Moreover, we showed that laminin-1 expression in the gut was increased in HD mice compared to controls. From these results, we hypothesized that excessive laminin is caused by an insufficiency or dysfunction of the receptors, that impairs interaction between ENCC and laminin, resulting in aganglionosis. To test this hypothesis, we examined the expression of β1 integrin, which is a receptor for laminin, in Ednrb KO mouse.The expression of β1 integrin was not significantly different between KO and WT in the gut. However, the β1-integrin expression in the isolated ENCC was significantly decreased in KO. Since integrin has a wide variety of ligands which have crucial roles in ENCCs migration, impairment of this interaction between integrin and its ligands may disturb normal ENS development, resulting in an aganglionic colon in this model.
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| Academic Significance and Societal Importance of the Research Achievements |
この実験は、ヒルシュスプルング病（H病）において、腸管培養中に付加する物質を変えることでその効果を試すことができるという、実験系としての将来性を秘めている。また今回ラミニン単独添加ではH病腸管において神経発達効果が得られなかったことから、レセプターの発現を調査しH病腸管で低下していることを明らかにした。今後はレセプターに着目することにより、今まで手術にしか根治し得ないとされてきたH病の治療に新たな風を吹き込むことが期待できる。実臨床では、便秘などの術後合併症がおこることがあるが、投薬による腸管神経伸長効果が実用化されれば、術後の補助療法としても、効果が期待できる。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Hirschsprung's disease in the laparoscopic transanal pull-through era: implications of age at surgery and technical aspects2018
Author(s)
Miyano G, Takeda M, Koga H, Okawada M, Nakazawa-Tanaka N, Ishii J, Doi T, Lane GJ, Okazaki T, Urao M, Yamataka A.
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Journal Title
J Pediatr Surg
Volume: 34
Issue: 2
Pages: 183-188
DOI
Related Report
Peer Reviewed
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