| Project/Area Number |
16K20585
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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 |
Surgical dentistry
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| Research Institution | Kyushu University |
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Principal Investigator |
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 粘膜類天疱瘡 / BP180 / 口腔癌 / 歯学 |
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| Outline of Final Research Achievements |
This project focused on BP180 as one of the autoantibody target antigens of the pemphigoid group and analyzed regulation mechanism of its expression. In the course of analysis, it was found that the basement membrane structure dissociation in pemphigoid was similar to that seen in cancer invasion.
Therefore, we further analyzed expression control of BP180 in oral cancer (gingival and tongue cancer) cells and tissue samples compared with normal tongue tissue, and we have identified that miR-203 is involved in p53-independent control of BP180 expression. Furthermore, the interaction among BP180, wild-type p53, mutant p53, and miR203 was analyzed in vitro (Yasukochi A et al., J Biochem, 2019)
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| Academic Significance and Societal Importance of the Research Achievements |
類天疱瘡群は、表皮真皮間結合部の接着機構であるヘミデスモソームを構成する分子に対する自己抗体が生じることにより表皮下水疱を生じる自己免疫性水疱症疾患であるが、その自己抗体の標的抗原は多彩であり、具体的な疾患発症に関わる責任抗原は明確となっていない。病態解明に結びつくBP180の機能解析の進捗が滞っている理由に、BP180の発現制御機構やそのリガンドが解明されていないことが挙げられる。
本研究によって明らかとなった、新規のBP180発現制御機構は、ヘミデスモソームの解離が病態の主体である類天疱瘡のほか、癌浸潤機構や創傷治癒機転の解明にもつながり、様々な疾患に対する新たな治療標的を提示した。
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