2019 Fiscal Year Final Research Report
AHR controls skin cancerization through metabolism of FICZ, a UVA-photosensitizer
Project/Area Number |
18K16036
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53050:Dermatology-related
|
Research Institution | Nagoya City University |
Principal Investigator |
Nakamura Motoki 名古屋市立大学, 医薬学総合研究院(医学), 講師 (70645051)
|
Project Period (FY) |
2018-04-01 – 2020-03-31
|
Keywords | 芳香族炭化水素受容体 / 紫外線 / UVB / UVA / アポトーシス / 皮膚癌 |
Outline of Final Research Achievements |
We observed activation of AHR and upregulation of CYP1A1 by FICZ, as well as induction of apoptosis by UVA-toxicity of FICZ itself. It was revealed that inhibition of AHR decreased CYP1A1 which metabolizes FICZ and increased apoptosis. It was proved that UVA-toxicity can be controlled by increasing / decreasing FICZ metabolism by AHR activity. UVA-toxicity of FICZ was also suppressed by CYP1A1 produced through AHR by UVB irradiation, and it was found that AHR inhibition increases UVA-induced apoptosis after UVB irradiation. Increased apoptosis leads to suppression of skin cancer. This is the innate mechanism of skin cancer suppression in our skin.
|
Free Research Field |
皮膚科学
|
Academic Significance and Societal Importance of the Research Achievements |
AHRによるFICZ/UVA毒性の制御と皮膚癌の発生の関連の証明は、紫外線発癌および職業性の発癌として知られるタールやアゾ色素、ヒ素の暴露による皮膚癌発症のメカニズムの解明につながる。また様々な疾患や皮膚老化の原因としてクローズアップされることの多いAHRの皮膚における重要な役割の発見であり、実用化の始まっているAHR阻害薬の外用薬等の汎用に警鐘を鳴らす。
|