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2020 Fiscal Year Final Research Report

Study on the role for epidermal Regnase-1 in regulation of skin inflammation and carcinogenesis.

Research Project

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Project/Area Number 18H02833
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionKochi University

Principal Investigator

Sano Shigetoshi  高知大学, 教育研究部医療学系臨床医学部門, 教授 (80273621)

Co-Investigator(Kenkyū-buntansha) 高石 樹朗  高知大学, 教育研究部医療学系臨床医学部門, 助教 (10303223)
山本 真有子  高知大学, 教育研究部医療学系臨床医学部門, 助教 (20423478)
森坂 広行  高知大学, 医学部附属病院, 医員 (60826840)
石元 達士  高知大学, 医学部附属病院, 医員 (40750039)
Project Period (FY) 2018-04-01 – 2021-03-31
Keywords皮膚炎症 / 皮膚癌 / 細胞内シグナル / 2段階発癌モデル / 紫外線誘発発癌モデル
Outline of Final Research Achievements

We explored the carcinogenesis of epidermal specific Regnase-1 knockout mice (Reg1-cKO) after UVB irradiation or chemical-induced protocol with DMBA/TPA. Strikingly, they developed skin tumors and squamous carcinoma at much earlier time points than controls. It has been recognized that the arachidonic acid/prostaglandin (AR/PG) pathway was involved in inflammation and carcinogenesis. Recent study revealed that Regnase-1 targeted COX2, which is a critical enzyme for the AR/PG pathway. Finally, topical treatment with COX2 inhibitor specifically suppressed the tumor promoter TPA-induced thickening of epidermis in Reg1-cKO. Taken together, Regnase-1 plays inhibitory roles not only for epidermal inflammation but also carcinogenesis. Also, its ablation leads to skin carcinogenesis via the AR/PG pathway.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本邦では急速な高齢化とともに、癌の発症頻度は増加傾向にある。化学物質や紫外線などに曝されている皮膚においては、高年齢化とともに炎症が皮膚癌に移行する例を日常診療で経験する。しかし、皮膚慢性炎症から発癌にいたる分子機構は解明されていなかった。我々の研究は、炎症の制御に関わるRegnase-1の表皮特異的ノックアウトマウスを用いて、炎症-発癌プロセスを解明できた。この知見をもとに、皮膚癌治療の創薬のために新たなヒントが得られるものと期待される。

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Published: 2022-01-27  

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