部位特異的な上皮間葉系相互作用を通じた皮膚疾患病態解明及び再生医療に関する研究

2008 Fiscal Year Annual Research Report

• Project/Area Number: 18689028
• Research Institution: Nagoya City University
• Principal Investigator: 山口 裕史 Nagoya City University, 大学院・医学研究科, 准教授 (00335340)
• Keywords: 線維芽細胞 / 表皮細胞 / メラノサイト / 再生医療 / 創傷治癒 / 皮膚癌 / 紫外線 / 悪性黒色腫

Research Abstract

「皮膚が場所により違うのは、真皮線維芽細胞という間葉系由来細胞が、最外層に存在する表皮細胞やメラノサイトに影響を及ぼすから」という独創的観点から多数の研究成果を揚げた。表皮のみを効率良く採取する方法を編み出し公表するなど、難治性皮膚潰瘍や皮膚がんに関する論文で、研究課題の再生医療を臨床応用する論文を発表した。基礎研穿においては、「ヒト成人においても、上皮間葉系相互作用(真皮線維芽細胞がその上にある上皮系細胞に与える作用)により部位特異性(皮膚のさまざまな部位で性質が異なること)を決定付けていること」を実証してきた。手のひら・足のうらの皮膚は、分厚い皮膚で外からの刺激に強い・毛が無い・色素が薄いという3つの特徴がある。表皮細胞(FAsEBJ)に及ぼすDickkopfl(DKK1)の影響をマイクロアレイによる解析を含めた分子生物学的手法を用いて更に詳しく調べた。手のひら・足のうらの真皮線維芽細胞で発現が高いDKKIが、メラノサイトの機能を抑えるだけでなく、表皮細胞のメラニン取り込み能を抑制すると同時に、重層化を促進している結果を得ることが出来た。また皮膚がん発症には部位特異性があり、露光部に多く、紫外線の影響を受けているものが多い。ヒト皮膚に関して色調を司る因子(紫外線や部位特異的なサイトカインの発現様式)の研究にも従事し、成果を上げた。またマウス毛包形成におけるDKK1を含めたWnt系、Shh系、Bmp系の相互作用も調べDKK1が制御するb-カテニン系の重要性を調べた。

Research Products

• [Journal Article] Embryonic hair follicle fate change by augmented betacatenin signaling thro ugh Shh and Bmp signaling (2009)
  • Author(s): Suzuki K, Yamaguchi Y, Villacorte M, Mihara K, Akiyama M, Shimizu H, Taketo MM, Nakagata N, Ts ukiyama 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 ight (308 nm) 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-t ype 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 seco nd trimester of pregnancy (2009)
  • Author(s): lshida I, Yamaguchi Y, Tanemura A, Hosokawa K, !tam' S, Morita A, Katayama I. (Co-first and Cor responding author)
  • Journal Title: Arch Dermatol (IN PRESS)
  • Peer Reviewed
• [Journal Article] al limb ischemia treated with cyclosporine and adjuvant sympathectomy (2009)
  • Author(s): K, Sano S, Morita Ad Katayama I. (Co-first and Corresponding aut hor)
  • Journal Title: Dermatol Surg (IN PRESS)
  • 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 (IN PRESS)
  • Peer Reviewed
• [Journal Article] Molecular basis of premature skin aging induced by tobacco smoking (2009)
  • Author(s): Morita A, Torii K, Maeda A, Yam aguchi Y
  • Journal Title: J Investig Dermatol Symp Proc (IN PRESS)
  • 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 (IN PRESS)
  • Peer Reviewed
• [Journal Article] Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting W nt/betacatenin signaling in keratinocytes (2008)
  • Author(s): Yamaguchi Y, Passeron T, Hoashi T, Watabe H, Rouzaud F, Yasum oto K, Hara T, Tohyama C, Katay ama I, Miki T, Hearing VJ. (Corr esponding author)
  • Journal Title: FASEB J 22(4) Pages: 1009-1020
  • Peer Reviewed
• [Journal Article] Melanin mediated apoptosis of epidermal cells damaged by ultraviolet radiati on : factors influencing the incidence of skin cancer (2008)
  • Author(s): Yamaguchi Y, Beer JZ, Hearing V J. (Corresponding author)
  • Journal Title: Arch Dermatol Res 300(Supplem ent 1) Pages: 43-50
  • Peer Reviewed
• [Journal Article] Establishment of suction blister roof grafting by injection of local anesthesia beneath the epidermis : less painful and more rapid formation of blisters (2008)
  • Author(s): Hanafusa T, Yamaguchi Y, Nakam ura M, Kojima R, Shima R, Furui Y, Watanabe S, Takeuchi A, Kan eko N, Shintani Y, Maeda A, Tani M, Morita A, Katayama I. (Co-fi rst and Corresponding author)
  • Journal Title: J Dermatol Sci 50(3) Pages: 243-247
  • Peer Reviewed
• [Journal Article] Cyclobutane pyrimidine dimer formation and p53 production in human skin a fter repeated UV exposure (2008)
  • Author(s): Yamaguchi Y, Coelho SG, Zmudz ka BZ, Takahashi K, Beer JZ, He aring VJ, Miller SA
  • Journal Title: Exp Dermatol 17(11) Pages: 916-924
  • Peer Reviewed
• [Journal Article] Dynamics of pigmentation induction by repeated UV exposures : dose, dose interval and UV spectrum dependence (2008)
  • Author(s): Miller SA, Coelho SG, Zmudzka B Z, Bushar HF, Yamaguchi Y, Hea ring VJ, Beer JZ
  • Journal Title: Br J Dermatol 159(4) Pages: 921-930
  • Peer Reviewed
• [Journal Article] Congenital peristernal dermal sinuses : a new entity? (2008)
  • Author(s): Kubo T, Takagi T, Yamaguchi Y, Yano K, Hosokawa K
  • Journal Title: Br J Dermatol 159(3) Pages: 763-765
  • Peer Reviewed
• [Journal Article] Apocrine adenocarcinoma originating from the Moll's gland of the eyelid : report of a case (2008)
  • Author(s): Kanazawa S, Kubo T, Tanag MA, Yamaguchi Y, Hoshida Y, Yano K, Hosokawa K
  • Journal Title: Eur J Plast Surg 31(6) Pages: 333-336
  • Peer Reviewed
• [Journal Article] Epithelioid sarcoma on the foot masquerading as an intractable wound
  • Author(s): Nishimura Y, Yamaguchi Y, Hama da K, Tomita Y, Maeda A, Morita A, Katayama I
  • Journal Title: Clin Exp Dermatol (IN PRESS)
  • Peer Reviewed
• [Presentation] Adult dermal fibroblasts determine the fate of the overlying epide rmis (2009)
  • Author(s): Yamaquchi Y
  • Organizer: The Global COE Liaison Laboratory regular seminar
  • Place of Presentation: Kumamoto, Japan
  • Year and Date: 2009-03-04
• [Presentation] The effect of UV on human skin pigmentation (2009)
  • Author(s): Yamaquchi Y
  • Organizer: 3^<rd> Annual Symposium in Institute of Dermatological Science
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2009-02-06
• [Presentation] Melanocyte biology (2009)
  • Author(s): Yamaquchi Y
  • Organizer: Preseminar for the 3^<rd> Annual Symposium in Institute of Dermatological Science
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2009-02-05
• [Presentation] Suction blister formation time reduction by subepidermal injection (2008)
  • Author(s): Yamaquchi Y, Hanafusa T, Nakamura M, Morita A
  • Organizer: IID 2008 (International Investigative Dermatology 200 81
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20080514-17
• [Presentation] CS-14 Molecular and surgical pathology (2008)
  • Author(s): Yamaguchi Y
  • Organizer: The 20th International Pigment Cell Conference and 5th International Melanoma Research Conference
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20080507-12
• [Presentation] Regulation of skin pigmentation and thickness by dickkopf 1 (DKK 1) (2008)
  • Author(s): Yamaguchi Y
  • Organizer: IID 2008 Satellite Symposium Photoaging Research Symposium
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2008-05-13
• [Book] 看護学テキストNiCE疾患論第17章皮膚疾患色素異常症 (2009)
  • Author(s): 山口裕史
  • Total Pages: 500
  • Publisher: 南光堂(Inpress)
• [Book] 1冊でわかる光皮膚科-皮膚科医に必須のPhotodermatology紫外線とメラノサイト (2009)
  • Author(s): 山口裕史
  • Total Pages: 232
  • Publisher: 文光堂
• [Remarks]
  • URL: http://read.jst.go.jp/