部位特異的な皮膚再生医療に関する研究

• Project/Area Number: 21591440
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nagoya City University
• Principal Investigator: 山口 裕史 Nagoya City University, 医学(系)研究科(研究院), 研究員 (00335340)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: メラノサイト / バイオインフォーマティクス / 表皮角化細胞 / 悪性黒色腫 / 線維芽細胞 / 表皮細胞 / 再生医療 / 創傷治癒 / 皮膚癌 / 紫外線

Research Abstract

メラノサイトは神経堤に由来し、胎生期に背部の神経管から腹側に向かって遊走することが知られているが、その遊走がどのようにしておこなわれているのかはほとんど明らかにされていない。我々は大学倫理委員会の承認のもと、堕胎された胎児の頭部、背部、腹部、足底の4か所から皮膚生検を行い、胎生期のメラノサイトの分化、遊走についてさまざまな解析を施行した。まず、同一個体から得た上記4ヶ所由来の凍結切片を用いてメラノサイトを標識する抗体を用いて免疫染色を行った。初期メラノソームの構成蛋白であるGp100の発現がチロシナーゼ、DCT、MART-1の発現に先行した。また、毛包のメラノサイトは真皮から直接供給されるのではなく、表皮を経由し供給されるということが分かった。また足底では、胎児メラノサイトは汗管開口部にのみ限局して存在しており、悪性黒色腫が皮丘より発症することとの関連性が示唆された。次に胎児メラノサイトを部位別に分離、培養したところHMB-45、αPEP-7h、αPEP-8h、Melan-Aでは染色されなくなり、Nestinでのみ染色されるようになった。しかし成人のケラチノサイト、線維芽細胞との共培養を行うと、HMB-45で陽性に染色されるようになった。培養によって未熟化した胎児メラノサイトがケラチノサイトや線維芽細胞からの何らかの因子により分化成熟したことが示されたが、部位による差異は確認できなかった。さらにマイクロアレイによって4か所の胎児メラノサイトの遺伝子発現解析を行った。その結果、足底由来のメラノサイトとその他の部位のメラノサイトの間で差異を再び認め、そのいくつかの遺伝子(bFGFなど)はウエスタンブロットによる蛋白レベルの解析によっても明らかな差を認めた。

Research Products

• [Journal Article] AMP kinase-related kinase NUAK2 affects tumor growth, migration and clinical outcome of human melanoma. (2011)
  • Author(s): Namiki T, Tanemura A, Valencia JC, Coelho SG, Passeron T, Kawaguchi M, Vieira WD, Ishikawa M, Nishijima W, Izumo T, Kaneko Y, Katayama I, Yamaguchi Y, Yin L, Polley EC, Liu H, Kawakami Y, Eishi Y, Takahashi E, Yokozeki H, Hearing VJ
  • Journal Title: Proc Natl Acad Sci USA Volume: 108(16) Pages: 6597-6602
  • Peer Reviewed
• [Journal Article] NADPH : quinine oxidoreductase-1 as a new regulatory enzyme that increases melanin synthesis. (2010)
  • Author(s): Yamaguchi Y, Hearing VJ, Maeda A, Morita A
  • Journal Title: J Invest Dermatol Volume: 130(3) Pages: 645-647
  • Peer Reviewed
• [Journal Article] Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome-specific and proteolytically released protein. (2010)
  • Author(s): Hoashi T, Sato S, Yamaguchi Y, Passeron T, Tamaki K, Hearing VJ
  • Journal Title: FASEB J Volume: 24(5) Pages: 1616-1629
  • Peer Reviewed
• [Journal Article] Good's syndrome (hypogammaglobulinemia with thymoma) presenting intractable opportunistic infections and hyperkeratotic lichen planus. (2010)
  • Author(s): Hanafusa T, Umegaki N, Yamaguchi Y, Katayama I
  • Journal Title: J Dermatol Volume: 37(2) Pages: 171-174
  • NAID: 10027065837
  • Peer Reviewed
• [Journal Article] Clinical implications of leukocytapheresis using a centrifugal cell separator for steroid-resistant pyoderma gangrenosum associated with inflammatory bowel diseases. (2010)
  • Author(s): Hanafusa T, Azukizawa H, Umegaki N, Tani M, Yamaguchi Y, Katayama I
  • Journal Title: J Dermatol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Epithelioid sarcoma on the foot masquerading as an intractable wound for > 18 years. (2010)
  • Author(s): Nishimura Y, Yamaguchi Y, Tomita Y, Hamada K, Maeda A, Morita A, Katayama I
  • Journal Title: Clin Exp Dermatol Volume: 35(3) Pages: 263-268
  • Peer Reviewed
• [Journal Article] NQO1 as an oxidoreductase enzyme that increases melanin synthesis (2010)
  • Author(s): Yamaguchi Y, Maeda A, Hearing VJ, Morita A.
  • Journal Title: J Invest Dermatol 130(3) Pages: 645-647
  • Peer Reviewed
• [Journal Article] Good's syndrome(hypogammaglobulinemia with thymoma)presenting intractable opportunistic infections and hyperkeratotic lichen planus (2010)
  • Author(s): Hanafusa T, Umegaki N, Yamaguchi Y, Katayama I.
  • Journal Title: J Dermatol 37(2) Pages: 171-174
  • NAID: 10027065837
  • Peer Reviewed
• [Journal Article] Glycoprotein nonmetastatic melanoma protein b(GPNMB), a melanocytic cell marker, is a melanosome-specific proteolytically released protein (2010)
  • Author(s): Hoashi T, Sato S, Yamaguchi Y, Passeron T, Tamaki K, Hearing VJ.
  • Journal Title: FASEB J (In Press, Epub ahead)
  • Peer Reviewed
• [Journal Article] Embryonic hair follicle fate change by augmented beta-catenin signaling through Shh and Bmp signaling (2009)
  • Author(s): Suzuki K, Yamaguchi Y, Villacorte M, Mihara K, Akiyama M, Shimizu H, Taketo MM, Nakagata N, Tsukiyama T, Yamaguchi TP, Kato S, Birchmeier W, Yamada G.
  • Journal Title: Development 136(3) Pages: 367-372
  • Peer Reviewed
• [Journal Article] The development of a filter to enhance the efficacy and safety of excimer light(308nm)therapy (2009)
  • Author(s): Kobayashi K, Yasuda Y, Shintani Y, Sumitomo T, Saga T, Kimura M, Yamamoto A, Mori T, Maeda A, Yamaguchi Y, Morita A.
  • Journal Title: Photodermatol Photoimmunol Photomed 25(1) Pages: 30-36
  • Peer Reviewed
• [Journal Article] Feasibility and accuracy of a newly developed hand-held device with a flat-type fluorescent lamp for measuring the minimal erythema dose for narrow-b and UVB therapy (2009)
  • Author(s): Morita A, Shintani Y, Nishida E, Kato H, Yoshida H, Minamoto M, Yamaguchi Y, Maeda A.
  • Journal Title: Photodermatol Photoimmunol Photomed 25(1) Pages: 41-44
  • Peer Reviewed
• [Journal Article] Stage III melanoma treated with chemotherapy after surgery during the second trimester of pregnancy (2009)
  • Author(s): Ishida I, Yamaguchi Y, Tanemura A, Hosokawa K, Itami S, Morita A, Katayama I.(Co-first and Corresponding author)
  • Journal Title: Arch Dermatol 145(3) Pages: 346-348
  • Peer Reviewed
• [Journal Article] Intractable wounds caused by pyoderma gangrenosum in a patient with critical limb ischemia treated with cyclosporine and adjuvant sympathectomy (2009)
  • Author(s): Takahashi Y, Yamaguchi Y, Itoh K, Sano S, Morita A, Katayama I.(Co-first and Corresponding author)
  • Journal Title: Dermatol Surg 35(4) Pages: 699-703
  • Peer Reviewed
• [Journal Article] Short- and long-term effects of ultraviolet radiation on the pigmentation of human skin (2009)
  • Author(s): Coelho SG, Choi W, Brenner M, Miyamura Y, Yamaguchi Y, Wolber R, Smuda C, Batzer J, Kolbe L, Ito S, Wakamatsu K, Zmudzka B, Beer JZ, Miller SA, Hearing VJ.
  • Journal Title: J Investig Dermatol Symp Proc 14(1) Pages: 32-35
  • Peer Reviewed
• [Journal Article] Molecular basis of premature skin aging induced by tobacco smoking (2009)
  • Author(s): Morita A, Torii K, Maeda A, Yamaguchi Y.
  • Journal Title: J Investig Dermatol Symp Proc 14(1) Pages: 53-55
  • Peer Reviewed
• [Journal Article] Regulation of skin pigmentation and thickness by dickkopf 1(DKK1) (2009)
  • Author(s): Yamaguchi Y, Morita A, Maeda A, Hearing VJ.
  • Journal Title: J Investig Dermatol Symp Proc 14(1) Pages: 73-75
  • Peer Reviewed
• [Journal Article] Epithelioid sarcoma on the foot masquerading as an intractable wound (2009)
  • Author(s): Nishimura Y, Yamaguchi Y, Hamada K, Tomita Y, Maeda A, Morita A, Katayama I.
  • Journal Title: Clin Exp Dermatol (IN PRESS, Epub)
  • Peer Reviewed
• [Journal Article] Physiological factors that regulate skin pigmentation (2009)
  • Author(s): Yamaguchi Y, Hearing VJ.
  • Journal Title: Biofactors 35(2) Pages: 193-199
  • Peer Reviewed
• [Journal Article] The effects of topically applied glycolic acid and salicylic acid on ultraviolet radiation-induced erythema, DNAdamage and sunburn cell formation in human skin (2009)
  • Author(s): Kornhauser A, Wei RR, Yamaguchi Y, Coelho SG, Kaidbey K, Barton C, Takahashi K, Beer JZ, Miller SA, Hearing VJ.
  • Journal Title: J Dermatol Sci 55(1) Pages: 10-17
  • NAID: 10025334045
  • Peer Reviewed
• [Presentation] Aiming for the ideal skin regenerative medicine via translational research (2009)
  • Author(s): Yamaguchi Y.
  • Organizer: JST-Swiss Federal Institute of Technology Zurich Seminar
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-11-05
• [Presentation] Aiming for the ideal skin regenerative medicine via translational research : adult dermal fibroblasts determine the fate of the overlying epidermis (2009)
  • Author(s): Yamaguchi Y.
  • Organizer: Laboratory of Cell Biology Seminar at National Cancer Institute, National Institutes of Health
  • Place of Presentation: Bethesda, MD, USA
  • Year and Date: 2009-09-01
• [Presentation] The expression of dickkopf 1(DKK1)in palmoplantar skin is upregulated in vivo (2009)
  • Author(s): Yamaguchi Y, Hearing VJ, Suzuki K, Yamada G, Morita A.
  • Organizer: The 15^<th> Annual Meeting of the PanAmerican Society for Pigment Cell Research
  • Place of Presentation: Memphis TN, USA
• [Book] 看護学テキストNiCE 疾患論 第17章 皮膚疾患 色素異常症 (2010)
  • Author(s): 山口裕史
  • Total Pages: 500
  • Publisher: 南光堂(In press)
• [Book] 新皮膚科レジデント戦略ガイド (2010)
  • Author(s): 山口裕史
  • Publisher: 診断と治療社(In press)
• [Book] からだと光の事典 (2010)
  • Author(s): 山口裕史
  • Publisher: 朝倉書店(In press)
• [Remarks]
  • URL: http://read.jst.go.jp/