Roles of the AHR-OVOL1 axis in barrier dysfunction of atopic dermatitis

• Project/Area Number: 17K10213
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kyushu University
• Principal Investigator: Tsuji Gaku 九州大学, 大学病院, 講師 (20423551)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アトピー性皮膚炎 / 芳香族炭化水素受容体 / Ovo-like 1 / ovo-like 1

Outline of Final Research Achievements

Aryl Hydrocarbon Receptor (AHR) acts as a transcription factor. It regulates a variety of biological responses. Recently, genome-wide association analysis of atopic dermatitis has identified Ovo-like 1 (OVOL1) as a susceptibility of atopic dermatitis; however, the functions of OVOL1in the skin have not been clear. We found that AHR regulates filaggrin expression via OVOL1, which is important for skin barrier function. Therefore, it is suggested that AHR ligands could be a therapeutic agent for atopic dermatitis.

Academic Significance and Societal Importance of the Research Achievements

アトピー性皮膚炎の治療において、タール療法・紫外線療法は有効な治療法であることが分かっていたがその詳細な機序はこれまで不明であった。今回の研究で、これらの治療が皮膚のダイオキシン受容体を活性化し、それによってOVOL1という遺伝子の発現が増加することによって、皮膚の状態が改善することが分かった。したがって、皮膚のダイオキシン受容体に働きかけて、より効率的にOVOL1の発現を増加させる化合物はアトピー性皮膚炎の新たな治療薬の候補になると考えられる。

Research Products

• [Journal Article] Metformin inhibits IL-1β secretion via impairment of NLRP3 inflammasome in keratinocytes: implications for preventing the development of psoriasis (2020)
  • Author(s): Tsuji Gaku、Hashimoto-Hachiya Akiko、Yen Vu Hai、Takemura Masaki、Yumine Ayako、Furue Kazuhisa、Furue Masutaka、Nakahara Takeshi
  • Journal Title: Cell Death Discovery Volume: 6 Issue: 1
  • DOI: 10.1038/s41420-020-0245-8
  • Peer Reviewed / Open Access
• [Journal Article] IL-4 Augments IL-31/IL-31 Receptor Alpha Interaction Leading to Enhanced Ccl 17 and Ccl 22 Production in Dendritic Cells: Implications for Atopic Dermatitis (2019)
  • Author(s): Miake Sho、Tsuji Gaku、Takemura Masaki、Hashimoto-Hachiya Akiko、Vu Yen Hai、Furue Masutaka、Nakahara Takeshi
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 16 Pages: 4053-4053
  • DOI: 10.3390/ijms20164053
  • Peer Reviewed / Open Access
• [Journal Article] Implications of tryptophan photoproduct FICZ in oxidative stress and terminal differentiation of keratinocytes (2019)
  • Author(s): Furue Masutaka、Uchi Hiroshi、Mitoma Chikage、Hashimoto-Hachiya Akiko、Tanaka Yuka、Ito Takamichi、Tsuji Gaku
  • Journal Title: Giornale Italiano di Dermatologia e Venereologia Volume: 154 Issue: 1 Pages: 37-41
  • DOI: 10.23736/s0392-0488.18.06132-1
  • Peer Reviewed
• [Journal Article] Therapeutic Agents with AHR Inhibiting and NRF2 Activating Activity for Managing Chloracne (2018)
  • Author(s): Furue Masutaka、Fuyuno Yoko、Mitoma Chikage、Uchi Hiroshi、Tsuji Gaku
  • Journal Title: Antioxidants Volume: 7 Issue: 7 Pages: 90-90
  • DOI: 10.3390/antiox7070090
  • Peer Reviewed
• [Journal Article] Glyteer, Soybean Tar, Impairs IL-4/Stat6 Signaling in Murine Bone Marrow-Derived Dendritic Cells: The Basis of Its Therapeutic Effect on Atopic Dermatitis (2018)
  • Author(s): Takemura Masaki、Nakahara Takeshi、Hashimoto-Hachiya Akiko、Furue Masutaka、Tsuji Gaku
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 4 Pages: 1169-1169
  • DOI: 10.3390/ijms19041169
  • Peer Reviewed / Open Access
• [Journal Article] Tryptophan photo-product FICZ upregulates AHR/MEK/ERK-mediated MMP1 expression: Implications in anti-fibrotic phototherapy (2018)
  • Author(s): Murai Mika、Yamamura Kazuhiko、Hashimoto-Hachiya Akiko、Tsuji Gaku、Furue Masutaka、Mitoma Chikage
  • Journal Title: Journal of Dermatological Science Volume: 91 Issue: 1 Pages: 97-103
  • DOI: 10.1016/j.jdermsci.2018.04.010
  • Peer Reviewed
• [Journal Article] Antioxidative Phytochemicals Accelerate Epidermal Terminal Differentiation via the AHR-OVOL1 Pathway: Implications for Atopic Dermatitis (2018)
  • Author(s): Furue M、Hashimoto-Hachiya A、Tsuji G
  • Journal Title: Acta Dermato Venereologica Volume: 98 Issue: 10 Pages: 918-923
  • DOI: 10.2340/00015555-3003
  • Peer Reviewed
• [Journal Article] The role of the OVOL1-OVOL2 axis in normal and diseased human skin. (2018)
  • Author(s): Tsuji G, Ito T, Chiba T, Mitoma C, Nakahara T, Uchi H, Furue M.
  • Journal Title: Tsuji G, Ito T, Chiba T, Mitoma C, Nakahara T, Uchi H, Furue M. J Dermatol Sci. Volume: 90 Issue: 3 Pages: 227-231
  • DOI: 10.1016/j.jdermsci.2018.02.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis. (2017)
  • Author(s): Tsuji G, Hashimoto-Hachiya A, Kiyomatsu-Oda M, Takemura M, Ohno F, Ito T, Morino-Koga S, Mitoma C, Nakahara T, Uchi H, Furue M.
  • Journal Title: Cell Death Dis. Volume: 8 Issue: 7 Pages: e2931-e2931
  • DOI: 10.1038/cddis.2017.322
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway. (2017)
  • Author(s): Hirano A, Goto M, Mitsui T, Hashimoto-Hachiya A, Tsuji G, Furue M.
  • Journal Title: Int J Mol Sci. Volume: 18 Issue: 9 Pages: 1948-1948
  • DOI: 10.3390/ijms18091948
  • Peer Reviewed / Open Access / Int'l Joint Research