| Project/Area Number |
16K08142
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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 |
Applied molecular and cellular biology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中川 好秋 京都大学, 農学研究科, 准教授 (80155689)
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| Research Collaborator |
Watanabe Bunta
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | benzoyl phenyl urea / 筋線維芽細胞 / 線維化症 / ガン浸潤転移 / 網膜変性疾患 / benzoylphenylurea / 細胞運動 / benzoyl phenylurea / ガン関連線維芽細胞 (CAF) / がン逡巡 / 0-NBD / ATIC / 昆虫表皮真皮細胞 / ガン関連線維芽細胞(CAF) / 扁平上皮ガン / ガン細胞浸潤 / 昆虫表皮真皮細胞初代培養 / 細胞・組織 / 昆虫 / 有機化学 / 癌 |
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| Outline of Final Research Achievements |
Benzoyl phenyl ureas (BPUs), insect molting inhibitors, are well known insecticide. The mode of action of BPUs has been revealed to be the inhibition of chitin synthesis. At the early stage of insect molting, the phenotype transition of dermoepidermal cells occurs. During this process, the dermoepidermal cells proliferate and cause morphological change from squamous cell to columnar-shaped cell. We speculated that epithelial-mesenchymal transition (EMT)-like phenotypic modulation occurs at this early stage and this change promotes the molting, and we also hypothesized that BPUs may suppress this change. Based on this hypothesis, we examined this possibility using mammalian culture cells. As a result, BPU derivatives significantly suppressed the collective invasion of cancer cells mediated by cancer associated fibroblasts and the EMT of retinal pigment epithelial cells, which is the cause of the onset of retinal degenerative disease, age-related macular degeneration (AMD).
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| Academic Significance and Societal Importance of the Research Achievements |
本研究でこれまで殺虫剤として使用されてきたBPUが筋線維芽細胞の機能発現に起因する疾患（線維化やガンの転移・浸潤）向けた創薬研究のシードに成りうることを明らかにした。線維化は慢性的炎症反応による線維増殖組織の発達（コラーゲン等の細胞外基質の過剰産生により形成）に起因し、正常な臓器・器官の機能障害を起こす。肝硬変や肺線維症が線維化疾患として良く知られているが、加齢黄斑変性(AMD)等の網膜変性疾患も網膜組織の線維化疾患である。
高齢化社会が進むに伴いAMD患者の増加が予想される。BPU類縁体はAMDの進展を抑制するため、新たなAMDに向けた予防・治療薬として発展する可能性が示唆された。
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