| Project/Area Number |
18K08259
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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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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
YANAGI Teruki 北海道大学, 大学病院, 助教 (50755973)
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| Co-Investigator(Kenkyū-buntansha) |
秦 洋郎 北海道大学, 医学研究院, 助教 (90399915)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ミトコンドリア / 角化 / 有棘細胞癌 / 紫外線 / 細胞死 / ノックアウトマウス / 紫外線発癌 |
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| Outline of Final Research Achievements |
We investigated the function of Drp1 in normal epidermis/keratinocytes using epidermis-specific Drp1 knockout (EKO) mice. Epidermal development in the EKO mice were indistinguishable from those in the wild-type (WT) mice. Ultrastructural analysis and immunohistochemistry revealed that the mitochondria of keratinocytes in the EKO mice were neither elongated nor constricted. Drp1 knockdown did not diminish the cell growth of normal human keratinocytes. Both in vivo and in vitro, UVB-induced apoptosis in the EKO epidermis and keratinocytes did not differ from that in the WT mice. In chronic UVB-irradiation, the loss of Drp1 sensitized the epidermis to the development of skin tumors. Clinically, Drp1 is expressed more highly in sun-exposed skin than in non-exposed skin in individuals under age 40, but not in those over age 60. In conclusion, EKO mice demonstrate that Drp1 is dispensable for the development and apoptosis of the epidermis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではミトコンドリアと表皮角化細胞の分化と発癌を中心に解析した。ミトコンドリア分裂因子Drp1欠損は表皮の発生・分化への影響は認められず、紫外線発癌を促進する可能性が示唆された。さらに、腫瘍細胞に対するDrp1のノックダウン実験では腫瘍細胞の増殖抑制作用が認められた。これらの結果はDrp1は表皮細胞の分化には直接には影響を与えないが、腫瘍を形成した場合には不可欠の分子になることが考えられた。これらの成果は、今まで十分に注目されてこなかったミトコンドリアと癌をターゲットとした新規治療戦略につながる可能性がある。
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