| Project/Area Number |
22K16282
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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 53050:Dermatology-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
Asano Nobuyuki 山口大学, 医学部附属病院, 講師 (50786100)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 縮毛症 / woolly hair / LIPH / C3orf52 / C3ORF52 / C末端 / 先天性縮毛症 / LIPH遺伝子 / C3ORF52遺伝子 |
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| Outline of Research at the Start |
まず、近年報告された常染色体劣性遺伝形式を示す先天性縮毛症の新たな原因遺伝子であるC3ORF52遺伝子に着目し、その発現タンパクの機能や局在を培養細胞レベルで解明する。また、日本人において既知の遺伝子変異が同定されなかった縮毛症患者の遺伝子解析からC3ORF52遺伝子変異が同定された場合に、この変異による発現・機能解析を行うことで、ヒトにおける毛髪の成長、毛包の分化における役割や意義をさらに明らかにする。
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| Outline of Final Research Achievements |
In this study, expression vectors of wild-type LIPH and five mutant LIPH proteins were generated and Western blotting was performed in an overexpression system in cultured cells. The results showed that the three mutant LIPH proteins were not secreted out of the cells at all. Next, an expression vector of wild-type C3orf52 was generated and co-immunoprecipitated with wild-type LIPH and mutant LIPH. The results showed that only the C-terminal mutation, V437Gfs*4, showed significantly-reduced affinity to C3orf52, while the binding ability of the other mutations was comparable to that of the wild type. Further co-IP assays showed that LIPH and C3orf52 interacted via their C-terminus. We also showed that C3orf52 was mainly expressed at the Henle’s layer in human hair follicles. Finally, we performed functional analysis for the effects of mutant LIPH on the downstream signaling pathways. We found that downstream TGFα secretion was markedly reduced in all the mutant LIPH analyzed.
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| Academic Significance and Societal Importance of the Research Achievements |
縮毛症は日本人で最も患者数の多い先天性毛髪疾患であり、その病態を解明することには大きな意義がある。本研究を通じ、LIPH遺伝子変異の性質が明らかになるとともに、LIPHとC3orf52との物理的および機能的関連性もかなり解明された。本研究により、将来的に本疾患に対する治療薬を開発するための重要な知見が得られたと考えられる。
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