Analysis of HB-EGF on the pathogenesis of psoriasis using tetracycline-inducible transgenic mice system.

• Project/Area Number: 19591311
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Ehime University
• Principal Investigator: SHIRAKATA Yuji Ehime University, 大学院・医学系研究科, 講師 (50226320)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 尋常性乾癬 / 遺伝子誘導 / HB-EGF / Amphiregulin / Tet-on / TG mouse / 乾癬

Research Abstract

本研究は、活性化STAT3 が乾癬病変の形成に重要な役割を果たすことから、STAT3 を活性化するEGF family の機能を明らかにすることにある。表皮において重要であるEGF Family のHB-EGFとAmphiregulin の遊離型と膜型の遺伝子誘導マウスをそれぞれ開発し、乾癬のモデルマウスとして有用か否かについて検討した。これらのマウスにドキシサイクリンを投与し、自然発症乾癬モデルマウスとなり得るか現在観察中である。また、創傷刺激を与えて乾癬病変が誘導できるか否かについての実験を準備中である。

Research Products

• [Journal Article] PPARgamma is an important transcription factor in 1alpha,25-dihydroxyvitamin D3-induced involucrin expression (2008)
  • Author(s): Dai X, Sayama K, Shirakata Y, Tokumaru S, Yang L, Tohyama M, Hirakawa S, Hanakawa Y, Hashimoto K
  • Journal Title: J Dermatol Sci 50 Pages: 53-60
• [Journal Article] The NF-kB, 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 Immunol 20 Pages: 901-9
• [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: 981-4
• [Journal Article] An intermediary role of proHB-EGF shedding in growth factor-induced c-Myc gene expression (2008)
  • Author(s): Nanba D, Inoue H, Shigemi Y, Shirakata Y, Hashimoto K, Higashiyama S
  • Journal Title: J Cell Physiol. 214 Pages: 465-73
• [Journal Article] An interme role of proHB-EGF shedding in growth factor-induced c-Myc gene expression (2008)
  • Author(s): Nanba D, Inoue H, Shigerni Y, Shirakata Y, et. al.
  • Journal Title: J Cell Physiol 214 Pages: 465-73
  • Peer Reviewed
• [Journal Article] PPARgamma is an important transcription factor in lalpha, 25-dihydroxyvitamin D3-induced in voilucrin expression (2008)
  • Author(s): Dai X, Sayama K, Shirakata Y, et. al.
  • Journal Title: J Drematol Sci 50 Pages: 53-60
  • Peer Reviewed
• [Journal Article] Epiregulin, a member of the EGF family, is over-expressed in psoriatic epidermis (2007)
  • Author(s): Shirakata Y, Kishimoto J, Tokumaru S, Yamasaki K, Hanakawa Y, Tohyama M, Sayama K, Hashimoto K
  • Journal Title: J Dermatol Sci 45 Pages: 69-72
  • NAID: 10019994988
• [Journal Article] Hair follicle regeneration using grafted rodent and human cells (2007)
  • Author(s): Ehama R, Ishimatsu-Tsuji Y, Iriyama S, Ideta R, Soma T, Yano K, Kawasaki C, Suzuki S, Shirakata Y, Hashimoto K, Kishimoto J
  • Journal Title: J Invest Dermatol 127(9) Pages: 2106-15
• [Journal Article] STAT5a/PPARgamma Pathway Regulates Involucrin Expression in Keratinocyte Differentiation (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: J Invest Dermatol 127(7) Pages: 1728-35
• [Journal Article] CXCL16 is a novel mediator of the innate immunity of epidermal keratinocytes (2007)
  • 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: 1095-1102
  • NAID: 10020108093
• [Journal Article] Human corneal epithelial cell proliferation by epiregulin and its cross-induction by other EGF family members (2007)
  • Author(s): Morita S, Shirakata Y, Shiraishi A, Kadota Y, Hashimoto K, Higashiyama S, Ohashi Y
  • Journal Title: Molecular Vision 13 Pages: 2119-2128
• [Journal Article] Human corneal epithelial cell proliferation by epiregulin and its cross-induction by other EGF family members (2007)
  • Author(s): Morita S, Shirakata Y, et. al.
  • Journal Title: Molecular Vision 13 Pages: 2119-2128
  • Peer Reviewed
• [Journal Article] Epiregulin,a member of the EGF family,is over-expressed in psoriatic epidermis (2007)
  • Author(s): Shirakata Y, Kishimoto J, et. al.
  • Journal Title: J Dermatol Sci 45 Pages: 69-72
  • NAID: 10019994988
  • Peer Reviewed
• [Journal Article] Hair follicle regeneration using grafted rodent and human cells (2007)
  • Author(s): Ehama R, Ishimatsu-Tsuji Y, Iriyama S, Ideta R, Soma T, Yano K, Kawasaki C, Suzuki S, Shirakata Y, et. al.
  • Journal Title: J Invest Dermatol 127 Pages: 2106-15
  • Peer Reviewed
• [Journal Article] STAT5a/PPARgamma Pathway Regulates Involucrin Expression Keratinocyte Differentiation (2007)
  • Author(s): Dai X, Sayama K, Shirakata Y, et. al.
  • Journal Title: J Invest Dermatol 127 Pages: 1728-35
  • 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 (2007)
  • Author(s): Nagai H, Tokumaru S, Sayama K, Shira kata Y, et. al.
  • Journal Title: J Dermatol 34 Pages: 523-530
  • Peer Reviewed
• [Journal Article] CXCLl6 is a novel mediator of the innate immunity of epidermal keratinocytes (2007)
  • Author(s): Tohyama M, Sayama K, Komatsuzawa H, Hanakawa Y, Shirakata Y, et. al.
  • Journal Title: Int Immunol 19 Pages: 1095-1102
  • 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 (2000)
  • Author(s): Nagai H, Tokumaru S, Sayama K, Shirakata Y, Hanakawa Y, Hirakawa S, Dai X, Tohyama M, Yang L, Hashimoto K
  • Journal Title: J Dermatol 34 Pages: 523-530
  • NAID: 10021306180
• [Presentation] Keratinocyte-specific SOCS3 knockout mice show clinical phenotypes similar to human psoriasis (2008)
  • Author(s): Shirakata Y, Yang L, et.al.
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Kyoto
• [Presentation] A new skin equivalent using de-epithelialized amnion membrane (2007)
  • Author(s): Shirakata Y, Yang L, Hashimoto K
  • Organizer: 8^<th> Congress of the German-Japanese Society of Dermatology
  • Place of Presentation: Yokohama
• [Presentation] PPAR-gamma is involved in 1.25-dihydroxyvitamin D3-induced beta-defensin-3 and cathelicidin expression in normal keratinocyte (2007)
  • Author(s): Dai X, Shirakata Y, et.al.
  • Organizer: 68^<th> Annual Meeting of the Society for Investigative Dermatology
  • Place of Presentation: Los Angeles
• [Presentation] Development of a new skin equivalent model using de-epithelialized amnion membrane (2007)
  • Author(s): Yang L, Shirakata Y et.al.
  • Organizer: 68^<th> Annual Meeting of the Society for Investigative Dermatology
  • Place of Presentation: Los Angeles
• [Presentation] Development of a new skin equivalent model using de-epithelialized amnion memtmebrance (2007)
  • Author(s): Yang L, Shirakata Y, et. al.
  • Organizer: 68^<th> Annual Meeting of the Society for Investigative Dermatology
  • Place of Presentation: Los Angeles