Regulation of keratinocyte differentiation and innate immunity by innate immune regulator Ubc13

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390297
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Ehime University
• Principal Investigator: SAYAMA Koji Ehime University, 大学院・医学系研究科, 准教授 (80187286)
• Co-Investigator(Kenkyū-buntansha): HIRAKAWA Satoshi 愛媛大学, 医学部附属病院, 講師 (50419511) ; HANAKAWA Yasushi 愛媛大学, 大学院・医学系研究科, 講師 (90284398)
• Project Period (FY): 2007 – 2009
• Keywords: 皮膚感染症 / 自然免疫

Research Abstract

The E2 polyubiquitin-conjugating enzyme Ubc13 is a mediator of innate immune reactions. We generated keratinocyte-specific Ubc13-deficient mice (Ubc13^<flox/flox>K5-Cre). At birth, the skin of the Ubc13^<flox/flox>K5-Cre mice was abnormally shiny and smooth ; in addition, the mice did not grow and died by postnatal day P2. Histological analysis showed atrophy of the epidermis with keratinocyte apoptosis. Immunohistochemical analyses revealed reduced proliferation, abnormal differentiation, and apoptosis of keratinocytes in the Ubc13^<flox/flox>K5-Cre mouse epidermis. In culture, Ubc13^<flox/flox>K5-Cre keratinocyte growth was impaired and spontaneous cell death occurred. Therefore, Ubc13 is essential for keratinocyte growth, differentiation, and survival.

Research Products

• [Journal Article] The influence of hepatic damage on serum soluble Fas ligand levels of patients with drug rashes (2009)
  • Author(s): Tohyama M, Shirakata Y, Sayama K, Hashimoto K.
  • Journal Title: Allergy Clin Immunol 123 Pages: 971-972
  • Peer Reviewed
• [Journal Article] IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression Eur J Immunol (2009)
  • Author(s): Tohyama M, Hanakawa Y, Shirakata Y, Dai X, Yang L, Hirakawa S, Tokumaru S, Okazaki H, Sayama K, Hashimoto K.
  • Journal Title: 39 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Malignant acanthosis nigricans with enhanced expression of fibroblast growth factor receptor 3 Acta Derm Venereol (2009)
  • Author(s): Hida Y, Kubo Y, Nishio Y, Murakami S, Fukumoto D, Sayama K, Hashimoto K, Arase S
  • Journal Title: 89 Pages: 435-437
  • Peer Reviewed
• [Journal Article] Living skin equivalents constructed using human amnions as a matrix J Dermatol Sci (2009)
  • Author(s): Yang L, Shirakata Y, Tokumaru S, Xiuju D, Tohyama M, Hanakawa Y, Hirakawa S, Sayama K Hashimoto K.
  • Journal Title: 56 Pages: 188-195
  • Peer Reviewed
• [Journal Article] Nodal lymphangiogenesis and metastasis: Role of tumor-induced lymphatic vessel activation in extramammary Paget's disease Am J Pathol (2009)
  • Author(s): Hirakawa S, Detmar M, Kerjaschki D, Nagamatsu S, Matsuo K, Tanemura A, Kamata N, Higashikawa K, Okazaki H, Kameda K, Nishida-Fukuda H, Mori H, Hanakawa Y, Sayama K, Shirakata Y, Tohyama M, Tokumaru S, Katayama I, Hashimoto K.
  • Journal Title: 175 Pages: 2235-48
  • Peer Reviewed
• [Journal Article] PPARgamma is an important transcription factor in 1 alpha (2008)
  • Author(s): Dai X, Sayama K, Shirakata Y, Tokumaru S, Yang L, Tohyama M, Hirakawa S, Hanakawa Y, Hashimoto K.
  • Journal Title: 25-dihydroxyvitamin D3-induced involucrin expression. J Dermatol Sci 50 Pages: 53-60
  • Peer Reviewed
• [Journal Article] The NF-kappaB, P38 MAPK and STAT1 pathways differentially regulate the dsRNA-mediated innate immune responses of epidermal keratinocytes. (2008)
  • Author(s): Dai X, Sayama K, Tohyama M, Shirakata Y, Yang L, Hirakawa S, Tokumaru S, Hashimoto K.
  • Journal Title: Int Immunology 20 Pages: 901-909
  • Peer Reviewed
• [Journal Article] A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity syndrome. (2008)
  • Author(s): Tohyama M, Shirakata Y, Sayama K, Hashimoto K.
  • Journal Title: Br J Dermatol 159 Pages: 981-984
  • Peer Reviewed
• [Journal Article] Increased resistance to cationic antimicrobial peptide LL-37 in methicillin-resistant strains of staphylococcus aureus J Antimicrob Chemother (2008)
  • Author(s): Ouhara K, Komatsuzawa H, Kawai T, Nishi H, Fujiwara T, Fujiue Y, Kuwabara M, Sayama K, Hashimoto K, Sugai M.
  • Journal Title: 61 Pages: 1266-1269
  • Peer Reviewed
• [Journal Article] STAT5a/PPAR gamma pathway regulates involucrin expression in keratinocyte differentiation J Invest Dermato (2007)
  • Author(s): Dai, X. Sayama, K. Shirakata, Y. Hanakawa, Y. Yamasaki, K. Tokumaru, S. Yang, L. Wang, X. Hirakawa, S. Tohyama, M. Yamauchi, T. Takashi, K. Kagechika, H., Hashimoto, K.
  • Journal Title: 127 Pages: 1728-1735
  • Peer Reviewed
• [Journal Article] Suppressor of cytokine signaling 3 negative regulation of signal transducer and activator of transcription 3 in platelet-derived growth factor-induced fibroblast migration J Dermatol (2007)
  • Author(s): Nagai, H. Tokumaru, S. Sayama, K. Shirakata, Y. Hanakawa, Y. Hirakawa, S. Dai, X. Tohyama, M. Yang, L. Hashimoto, K.
  • Journal Title: 34 Pages: 523-530
  • Peer Reviewed
• [Journal Article] CXCL 16 is a novel mediator of the innate immunity of epidermal keratinocytes Int Immunol (2007)
  • Author(s): Tohyma, M. Sayama, K. Komatsuzawa, H. Hanakawa, Y. Shirakata, Y. Dai, X. Yang, L. Tokumaru, S. Nagai, H. Hirakawa, S. Sugai, M., Hashimoto, K.
  • Journal Title: 19 Pages: 1095-1102
  • Peer Reviewed
• [Presentation] Inflammatory mediator TAK1 regulates hair follicle cycling The 69th Annual Meeting of Society for Investigative Dermatology (2009)
  • Author(s): Sayama K, Shirakata Y, Ishimatsu-Tsuji Y, Kajiya K, Hirakawa S, Sugawara K, Chambon P, Akira S, Paus R, Kishimoto J, Hashimoto K.
  • Organizer: Montreal, CANADA
  • Year and Date: 20090506-20090509
• [Presentation] Conditional ablation of Ubc 13, a mediator of innate immunity, in keratinocytes induces abnormal differentiation (2008)
  • Author(s): Sayama, K. Yamamoto, M. Hanakawa, Y. Shirakata, Y. Akira, S., Hashimoto, K.
  • Organizer: decreased proliferation, and apoptosis. International Investigative Dermatology
  • Place of Presentation: Kyoto
  • Year and Date: 20080514-20080517
• [Presentation] The innate immunity mediator Ubc13-TAK1 is a master regulator of epidermal structure and apoptosis (2008)
  • Author(s): Sayama, K.
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Kyoto
  • Year and Date: 20080514-20080517
• [Presentation] TAK1 regulates hair follicle development in EDA receptor signaling 37th Annual European Society for Dermatological Research(ESDR)Meeting (2007)
  • Author(s): Sayama, K. Kajiya, K. Shirakata, Y. Hanakawa, Y. Hirakawa, S. Akira, S. Kishimoto, J. Hashimoto, K.
  • Organizer: Zurich, Switzerland
  • Year and Date: 20070905-20070908
• [Presentation] Ablation of TAK1 in mouse keratinocytes disturbed hair follicle development 68th Annual Meeting of the Society for Investigative Dermatology (2007)
  • Author(s): Sayama, K. Kajiya, K. Shirakata, Y. Hanakawa, Y. Hirakawa, S. Dai, X. Nagai, H. Akira, S. Kishimoto, J., Hashimoto, K.
  • Organizer: Los Angeles
  • Year and Date: 20070509-20070512