| Project/Area Number |
16H05367
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Gifu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
原 明 岐阜大学, 大学院医学系研究科, 教授 (10242728)
青木 仁美 岐阜大学, 大学院医学系研究科, 講師 (10550361)
本橋 力 岐阜大学, 大学院医学系研究科, 講師 (40334932)
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| Research Collaborator |
TAGUCHI Nobuhiko
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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 |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 色素細胞幹細胞 / 毛包ケラチノサイト幹細胞 / 幹細胞ニッシェ / プロテオーム / 表皮ケラチノサイト / ニッシェ / ノックアウトマウス / X線 |
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| Outline of Final Research Achievements |
HMBG2 gene has been identified as a novel MSC niche factor as a result of the following results. HMGB2 knockout mice did not show any increase in white hair compared to wild-type even when reared for a long time under normal rearing conditions, however, by 5 Gy X-ray irradiation, hair graying was significantly promoted in comparison with the irradiated controls. In addition, immunostaining of the epidermis of HMGB2 knockout mice after irradiation revealed the increase of γH2X, a marker for DNA damage of keratinocytes. It was also confirmed that knockdown of HMGB2 in cultured human keratinocytes increased cell death after irradiation, accumulated DNA damage, and further attenuated the antioxidant activity measured by mitochondrial activity. These results suggest that HMGB2 plays an important antioxidant role in cells, which is important for maintenance of MSC under stress environment, and serve as a MSC niche factor of the folliclar keratinocyte.
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| Academic Significance and Societal Importance of the Research Achievements |
色素細胞幹細胞（MSC）のニッシェの実体を機能的に解明することで，色素細胞の分化制御が可能になり，白髪や白斑症の証拠に基づいた治療・予防が可能になる。さらに、我々が探索する分子は成体のケラチノサイトにおいて放射線により発現が明確に変化する分子であり，その機能を遺伝子破壊により確かめることで培養細胞による従来の放射線の評価実験では明らかにできなかった放射線の新しい生物効果を解明できる可能性がある。
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