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

Research Project

Project/Area Number 19390297
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionEhime 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
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2009: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2008: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2007: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords皮膚感染症 / 自然免疫 / 角化細胞 / 細胞内シグナル / Ubc13 / NF-kB / ノックアウトマウス / アポトーシス / 分化 / MAP kinase / NF-кB / ユビキチン / TAK1 / cre-recombinase / 皮膚
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.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (27 results)

All 2009 2008 2007

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (8 results)

  • [Journal Article] The influence of hepatic damage on serum soluble Fas ligand levels of patients with drug rashes2009

    • Author(s)
      Tohyama M, Shirakata Y, Sayama K, Hashimoto K.
    • Journal Title

      Allergy Clin Immunol 123

      Pages: 971-972

    • Related Report
      2009 Final Research Report
    • 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 Immunol2009

    • 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

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Malignant acanthosis nigricans with enhanced expression of fibroblast growth factor receptor 3 Acta Derm Venereol2009

    • Author(s)
      Hida Y, Kubo Y, Nishio Y, Murakami S, Fukumoto D, Sayama K, Hashimoto K, Arase S
    • Journal Title

      89

      Pages: 435-437

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Living skin equivalents constructed using human amnions as a matrix J Dermatol Sci2009

    • 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

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nodal lymphangiogenesis and metastasis: Role of tumor-induced lymphatic vessel activation in extramammary Paget's disease Am J Pathol2009

    • 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

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression2009

    • Author(s)
      Tohyama M, et al.
    • Journal Title

      Eur J Immunol 39

      Pages: 11-10

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Living skin equivalents constructed using human amnion as a matrix2009

    • Author(s)
      Yang L, et al.
    • Journal Title

      J Dermatol Sci 56

      Pages: 188-195

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nodal lymphangiogenesis and metastasis : Role of tumor-induced lymphatic vessel activation in extramammary Paget's disease2009

    • Author(s)
      Hirakawa S, et al.
    • Journal Title

      Am J Pathol 175

      Pages: 2235-48

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PPARgamma is an important transcription factor in 1 alpha2008

    • 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

    • Related Report
      2009 Final Research Report
    • 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

    • Related Report
      2009 Final Research Report
    • 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

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased resistance to cationic antimicrobial peptide LL-37 in methicillin-resistant strains of staphylococcus aureus J Antimicrob Chemother2008

    • 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

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] PPARgamma is an important transcription factor in 1alpha, 25-dihydroxyvitamin D3-induced involucrin expression2008

    • Author(s)
      Dai, X. Sayama, K. Shirakata, Y. Tokumaru, S. YangL. Tohyama, M. Hirakawa, S. Hanakawa, Y., Hashimoto, K.
    • Journal Title

      J Dermatol Sci 50

      Pages: 53-60

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The NF-kappaB, P38MAPK and STAT1 pathways differentially regulate the dsRNA-mediated innate immune responses of epidemal keratinocytes.2008

    • Author(s)
      Dai, X. Sayama, K. Tohyama. M. Shirakata, Y. Yang, L. Hirakawa, S, Todumaru, S., Hashimoto, K.
    • Journal Title

      Int Immunology 20

      Pages: 901-909

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] STAT5a/PPAR gamma pathway regulates involucrin expression in keratinocyte differentiation J Invest Dermato2007

    • 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

    • Related Report
      2009 Final Research Report
    • 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 Dermatol2007

    • 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

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] CXCL 16 is a novel mediator of the innate immunity of epidermal keratinocytes Int Immunol2007

    • 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

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] STAT5a/PPARgamma pathway regulates involucrin expression in keratinocyte differentiation2007

    • 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

      J Invest Dermatol 127

      Pages: 1728-35

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CXCL16 is a novel mediator of the innate immunity of epidermal keratinocytes2007

    • Author(s)
      Tohyama 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

      Int Immunol 19

      Pages: 1095-102

    • NAID

      10020108093

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Inflammatory mediator TAK1 regulates hair follicle cycling The 69th Annual Meeting of Society for Investigative Dermatology2009

    • 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
    • Related Report
      2009 Final Research Report
  • [Presentation] Inflammatory mediator TAK1 regulates hair follicle cycling2009

    • Author(s)
      Sayama K, et al.
    • Organizer
      The 69^<th> Annual Meeting of Society for Investigative Dermatology
    • Place of Presentation
      Montreal, CANADA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Conditional ablation of Ubc 13, a mediator of innate immunity, in keratinocytes induces abnormal differentiation2008

    • 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
    • Related Report
      2009 Final Research Report
  • [Presentation] The innate immunity mediator Ubc13-TAK1 is a master regulator of epidermal structure and apoptosis2008

    • Author(s)
      Sayama, K.
    • Organizer
      International Investigative Dermatology
    • Place of Presentation
      Kyoto
    • Related Report
      2009 Final Research Report
  • [Presentation] Conditional ablation of Ubc 13, a mediator of innate immunity, in keratinocytes induces abnomaldifferentiation, decreased proliferation, and apoptosis.2008

    • Author(s)
      Sayama, K. Yamamoto, M. Hanakawa, Y. Shirakata, Y. Akira, S., Hashimoto, K.
    • Organizer
      International Investigative Dermatology
    • Place of Presentation
      Kyoto
    • Related Report
      2008 Annual Research Report
  • [Presentation] Ablation of TAK1 in mouse keratinocytes disturbed hair follicle development 68th Annual Meeting of the Society for Investigative Dermatology2007

    • 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
    • Related Report
      2009 Final Research Report
  • [Presentation] TAK1 regulates hair follicle development in EDA receptor signaling 37th Annual European Society for Dermatological Research(ESDR)Meeting2007

    • Author(s)
      Sayama, K. Kajiya, K. Shirakata, Y. Hanakawa, Y. Hirakawa, S. Akira, S. Kishimoto, J. Hashimoto, K.
    • Organizer
      Zurich, Switzerland
    • Related Report
      2009 Final Research Report
  • [Presentation] Ablation of TAK1 in mouse keratinocytes disturbed hair follicle development2007

    • Author(s)
      Sayama, K.Kajiya, K.Shirakata, Y.Hanakawa, Y.Hirakawa, S.Dai, X.Nagai, H.Akira, S.Kishimoto, J.and Hashimoto, K.
    • Organizer
      68^h Annual Meeting of the Society for Investigative Dermatology
    • Place of Presentation
      Los Angeles
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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