Dynamic epigenetic change of keratinocytes in inflammtory skin diseases

• Project/Area Number: 26461657
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nagoya University
• Principal Investigator: Yasushi Ogawa 名古屋大学, 医学部附属病院, 助教 (10567754)
• Research Collaborator: AKIYAMA Masashi 名古屋大学, 大学院医学系研究科, 教授 (60222551)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 皮膚科学 / ケラチノサイト / エピジェネティクス / 乾癬 / アトピー性皮膚炎

Outline of Final Research Achievements

This study aimed to investigate the roles of epigenetic changes of keratinocytes in the formation of inflammatory skin lesion of psoriasis. A reverse chemical genomics-approach was adopted. Topical imiquimod-induced skin inflammation was used as a mouse model of psoriasis, and various chemical inhibitors of chromatin modifying enzymes are applied to investigate their effect on the formation of the skin lesion. As a result we newly identified a histone demethylase inhibitor that promote the formation of the lesion, and a kinase inhibitor that suppress the skin lesion.

Research Products

• [Journal Article] Pityriasis rubra pilaris type V as an auto inflammatory disease by CARD14 mutations. (2017)
  • Author(s): Takeichi T, Sugiura K, Nomura T, Sakamoto T, Ogawa Y, Oiso N, Futei Y, Fujisaki A, Koizumi A, Aoyama Y, Nakajima K, Hatano Y, Hayashi K, Akemi Ishida-Yamamoto A, Fujiwara S, Sano S, Iwatsuki K, Kawada A, Suga Y, Shimizu H, McGrath JA, Akiyama M.
  • Journal Title: JAMA Dermatol Volume: 153 Issue: 1 Pages: 66-70
  • DOI: 10.1001/jamadermatol.2016.3601
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] IgE-independent pathophysiology of severe atopic dermatitis demonstrated in an IgE-deficient patient. (2016)
  • Author(s): Ogawa Y, Kono M, Tsujikawa M, Tsujiuchi H, Akiyama M.
  • Journal Title: J Dermatol Sci. Volume: - Issue: 2 Pages: 139-141
  • DOI: 10.1016/j.jdermsci.2016.01.008
  • Peer Reviewed
• [Journal Article] Revertant Mutation Releases Confined Lethal Mutation, Opening Pandora' s Box : A Novel Genetic Pathogenesis (2014)
  • Author(s): Ogawa Y, Takeichi T, Kono M, Hamajima N, Yamamoto T, Sugiura K, Akiyama M
  • Journal Title: PLoS Genet Volume: 10(5) Issue: 5 Pages: e1004276-e1004276
  • DOI: 10.1371/journal.pgen.1004276
  • Peer Reviewed / Open Access
• [Journal Article] A palindromic motif in the -2084 to -2078 upstream region is essential for ABCA12 promoter function in cultured human keratinocytes (2014)
  • Author(s): Shimizu Y, Ogawa Y, Sugiura K, Takeda J, Sakai-Sawada K, Yanagi T, Kon A, Sawamura D, Shimizu H, Akiyama M
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 6737-6737
  • DOI: 10.1038/srep06737
  • Peer Reviewed / Open Access
• [Presentation] Identification of an Palindromic Motif in the Upstream Region of ABCA12 required for Promoter Activity in Cultured Human Keratinocytes (2015)
  • Author(s): Yoshitaka Shimizu, Yasushi Ogawa (presenter), Kazumitsu Sugiura, Jun-ichi Takeda, Kaori Sakai-Sawada, Teruki Yanagi, Atsushi Kon, Daisuke Sawamura, Hiroshi Shimizu, Masashi Akiyama
  • Organizer: 日本研究皮膚科学会第４０回年次学術大会・総会
  • Place of Presentation: 岡山コンベンションセンター（岡山県岡山市）
  • Year and Date: 2015-12-11
• [Presentation] Revertant Mutation Releases Confined Lethal Mutation, Opening Pandora’s Box: A Novel Genetic Pathogenesis (2015)
  • Author(s): Yasushi Ogawa, Takuya Takeichi, Michihiro Kono, Nobuyuki Hamajima, Toshimichi Yamamoto, Kazumitsu Sugiura and Masashi Akiyama
  • Organizer: 日本研究皮膚科学会第４０回年次学術大会・総会
  • Place of Presentation: 岡山コンベンションセンター（岡山県岡山市）
  • Year and Date: 2015-12-11
  • Invited
• [Presentation] Reversion-triggered release of confined lethal mutations: an unreported genetic pathogenesis (2014)
  • Author(s): Yasushi Ogawa, Takuya Takeichi, Michihiro Kono, Nobuyuki Hamajima, Toshimichi Yamamoto, Kazumitsu Sugiura and Masashi Akiyama
  • Organizer: 44th meeting of the European Society for Dermatological Research
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-09-11 – 2014-09-12