The study of relationship between stress response and pathogenesis of Hailey Hailey disease using cell culture model

• Project/Area Number: 15K19707
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Kurume University
• Principal Investigator: MATSUDA Mitsuhiro 久留米大学, 医学部, 助教 (70569368)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ヘイリーヘイリー病 / 疾患モデル / 三次元培養 / RNAi / 小胞体ストレス / ゴルジ体ストレス

Outline of Final Research Achievements

The precise mechanism of development of skin lesions in Hailey-Hailey disease (HHD) remains unclear, mainly because of difficulty in obtaining skin samples due to the rarity of HHD and lack of an animal model. In this study, we generated 3D culture models using primary keratinocytes derived from an HHD patient and keratinocytes in which ATP2C1 mRNA was down-regulated with the RNAi method. Furthermore, we showed that endoplasmic reticulum and golgi stress may contribute to the pathogenesis of this disease.

Research Products

• [Journal Article] Superficial epidermolytic ichthyosis concomitant with atopic dermatitis (2018)
  • Author(s): Shimada H, Takeo N, Saito-Shono T, Ishikawa K, Sakai T, Goto M, Hatano Y, Fujiwara S, Matsuda M, Hamada T, Nakama T, Hashimoto T, Kono M, Akiyama M, Kitajima Y
  • Journal Title: Eur J Dermatol Volume: 28(1) Pages: 94-96
  • Peer Reviewed
• [Journal Article] A Case of Hailey-Hailey Disease with a Novel Nonsense Mutation in the ATP2C1 Gene (2017)
  • Author(s): Yasuda H, Kanazawa N, Matsuda M, Hamada T, Furumura M, Hashimoto T, Nakama T, Furukawa F
  • Journal Title: Ann Dermatol Volume: 29(5) Pages: 642-644
  • Peer Reviewed
• [Journal Article] Two novel missense mutations of STS gene underlie X-linked recessive ichthyosis: understanding of the mutational and structural spectrum. (2016)
  • Author(s): Oyama N, Matsuda M, Hamada T, Numata S, Teye K, Hashimoto T, Hasegawa M.
  • Journal Title: J Eur Acad Dermatol Venereol. Volume: 30(9) Issue: 9 Pages: 1629-31
  • DOI: 10.1111/jdv.13231
  • Peer Reviewed
• [Journal Article] Functional study of TGM1 missense mutations in autosomal recessive congenital ichthyosis. (2016)
  • Author(s): Numata S, Teye K, Karashima T, Matsuda M, Hamada T, Hashimoto T.
  • Journal Title: Exp Dermatol. Volume: 25(8) Issue: 8 Pages: 657-9
  • DOI: 10.1111/exd.13000
  • Peer Reviewed
• [Journal Article] A compound synonymous mutation c.474G>A with p.Arg578X mutation in SPINK5 causes splicing disorder and mild phenotype in Netherton syndrome. (2016)
  • Author(s): Numata S, Teye K, Krol RP, Okamatsu Y, Hashikawa K, Matsuda M, Fortugno P, Di Zenzo G, Castiglia D, Zambruno G, Hamada T, Hashimoto T.
  • Journal Title: Exp Dermatol. Volume: 25(7) Issue: 7 Pages: 568-70
  • DOI: 10.1111/exd.13011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anti-early endosome antigen 1 autoantibodies were detected in a pemphigus-like patient but not in the majority of pemphigus diseases. (2016)
  • Author(s): Nishikawa R, Takahashi H, Matsuda M, Imaoka K, Ogawa M, Teye K, Tsuchisaka A, Koga H, Komorowski L, Probst C, Hachiya T, Fritzler MJ, Ishii N, Ohata C, Furumura M, Krol RP, Muro Y, Morita E, Hashimoto T
  • Journal Title: Exp Dermatol Volume: 25 Issue: 5 Pages: 369-371
  • DOI: 10.1111/exd.12981
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Corneodesmosin gene deletion is prevalent in Japanese patients with peeling skin disease: identification of 2 new cases. (2016)
  • Author(s): Teye K, Suga Y, Numata S, Ishii N, Krol RP, Ohata C, Matsuda M, Honma M, Ishida-Yamamoto A, Hamada T, Hashimoto T.
  • Journal Title: Journal of Dermatological Science Volume: 82 Issue: 2 Pages: 134-137
  • DOI: 10.1016/j.jdermsci.2016.01.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A three-dimensional in vitro culture model of Hailey-Hailey disease. (2015)
  • Author(s): Matsuda M, Hamada T, Numata S, Teye K, Ishii N, Ohata C, Furumura M, Nakama T, Hashimoto T
  • Journal Title: Exp Dermatol Volume: 24 Issue: 10 Pages: 788-789
  • DOI: 10.1111/exd.12777
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Loss of heterozygosity in a case of glomuvenous malformations. (2015)
  • Author(s): Ohata C, Matsuda M, Hamada T, Shintani T, Muto I, Nagata H, Furumura M, Nakama T
  • Journal Title: J Dermatol Volume: 印刷中 Issue: 6 Pages: 646-647
  • DOI: 10.1111/1346-8138.12849
  • Peer Reviewed
• [Journal Article] Mutation study for 9 genes in 23 unrelated patients with autosomal recessive congenital ichthyosis in Japan and Malaysia. (2015)
  • Author(s): Numata S, Teye K, Krol RP, Karashima T, Fukuda S, Matsuda M, Ishii N, Furumura M, Ohata C, Saminathan SD, Ariffin R, Pramono ZA, Leong KF, Hamada T, Hashimoto T
  • Journal Title: J Dermatol Sci Volume: 78 Issue: 1 Pages: 82-85
  • DOI: 10.1016/j.jdermsci.2015.02.006
  • Peer Reviewed / Int'l Joint Research