| Project/Area Number |
17K15543
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | University of Yamanashi |
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Principal Investigator |
IWANO Tomohiko 山梨大学, 大学院総合研究部, 助教 (10442930)
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| Research Collaborator |
TAKEDA Sen
ZHU Maobi
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 卵管上皮 / エストロゲン / EGFR / Notch / 繊毛細胞 / 発生・分化 |
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| Outline of Final Research Achievements |
The lumen of the fallopian tube (FT) is lined with columnar epithelium composed of secretory and ciliated cells, both of which are important for reproduction. However, the molecular mechanism regulating the cell fate remains controversial. In this study, we established a primary culture system using porcine fallopian tube epithelial cells (FTECs) to study the differentiation mechanism. I found that estrogen promoted the differentiation of multi-ciliated cells (MCCs) through estrogen receptor β, following the reduction of DLL1, a ligand of Notch. Meanwhile, epidermal growth factor (EGF), a regulator of epithelial homeostasis and differentiation, suppressed ciliogenesis by the activation of Notch signaling. However, the estrogen pathway did not affect the activation of the EGF pathway. Taken together, the differentiation of MMCs in FT depends on the balance of EGF and estrogen signaling, either of which inhibits or stimulates the Notch signaling pathway respectively.
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| Academic Significance and Societal Importance of the Research Achievements |
卵管上皮ホメオスタシス維持機構における繊毛細胞分化の分子機構の一端が明らかになった。この成果は発生生物学的に重要な知見となり、再生医療の面でもiPS細胞からのin vitro分化誘導に働くキーファクター候補を提示できるという意義も有している。また、卵巣癌の一種は卵管上皮細胞の異常増殖および転移によると考えられており、本研究で着目したNotchやEGFシグナルの制御異常は他の組織ではガン化のリスクを高めることが知られているため、卵管上皮由来卵管がんの研究の基盤となることが期待される。
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