Regulation of keratinocyte differentiation and innate immunity by innate immune regulator Ubc13
Project/Area Number |
19390297
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Dermatology
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Research Institution | Ehime University |
Principal Investigator |
SAYAMA Koji Ehime University, 大学院・医学系研究科, 准教授 (80187286)
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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)
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Project Period (FY) |
2007 – 2009
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Project Status |
Completed (Fiscal Year 2009)
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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.
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Report
(4 results)
Research Products
(27 results)
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[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.
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[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.
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Journal Title
J Dermatol Sci 50
Pages: 53-60
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Peer Reviewed
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[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.
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Journal Title
Int Immunology 20
Pages: 901-909
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Peer Reviewed
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[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.
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[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.
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Peer Reviewed
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[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.
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[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.
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Journal Title
J Invest Dermatol 127
Pages: 1728-35
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Peer Reviewed
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[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
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Journal Title
Int Immunol 19
Pages: 1095-102
NAID
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Peer Reviewed
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[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
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[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
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[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
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[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
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[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