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

2007 Fiscal Year Annual Research Report

• Project/Area Number: 18689028
• Research Institution: Nagoya City University
• Principal Investigator: 山口 裕史 Nagoya City University, 名古屋市立大学・大学院・医学研究科, 准教授 (00335340)
• Keywords: 部位特異性 / 上皮間葉系相互作用 / 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」という独創的な立場・観点から多数の研究成果を揚げた。私は3年前にStanford大学Howard Y.Changから招聘されたので,この独創的な概念の講演をした。本年度彼らのグループは,NatureやCellに同様の成果を公表し,「今までジャンクとされていたNon-codingRNAが皮膚真皮線維芽細胞において,その場にふさわしい組織に分化・形質を維持するのに重要な働きをしていること」を証明した。私も臨床論文(特に難治性皮膚潰瘍や皮膚癌に関する論文で,研究課題の再生医療を臨床応用するもの)を公表する傍ら,同様の基礎研究を地道に行ってきた。「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具なること)を決定付けていること」を実証してきた。具体的には,メラノサイトに焦点を向け本年度のJ Biol Chemの総説特集号のカバーを飾った。またメラノサイト(J Invest DermatolというNature Publishing Groupの皮膚科領域で一番Impact factorの高い雑誌)および表皮細胞(FASEB J)に及ぼすDickkopf 1 (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、ともにFirst及びCorrespondingで論文発表した。また皮膚癌発症にも部位特異性があり,露光部に多く紫外線の影響を多分に受けているものが多い。人種間の皮膚癌発生頻度の差を比較検討することから,新しい皮膚癌発症機序を提唱し続けた。このような一連のヒト皮膚に関する色調を司る因子(紫外線や部位特異的なサイトカインの発現様式)についての総説執筆にも参加した。また最後に部位特異性を応用した難治性潰瘍治療法開発から派生した研究が実際の臨床でも活かされ,数々の潰瘍治療に役立った。更に多数の研究成果を来年度も揚げる事ができればと努力している。(782字)

Research Products

• [Journal Article] Involvement of dynein and spectrin with early melanosome transport and melanosomal protein trafficking.[Selected as Journal Cover] (2008)
  • Author(s): Watabe H, Valencia J, Le Pape E, Yamaguchi Y, Nakamura M, Rouzaud F, Hoashi T, Kawa Y, Mizoguchi M, Hearing VJ.
  • Journal Title: J Invest Dermatol 128(1) Pages: 162-174
  • Peer Reviewed
• [Journal Article] The effects of dickkopf 1 on keratinocyte gene profiles and on Wnt/-catenin signaling pathways:the mechanisms by which dickkopf 1 reduces cell/cell contact and melanosome transfer (2008)
  • Author(s): Yamaguchi Y(Corresponding author), Passeron T, Watabe H, Hoashi T, Rouzaud F, Yasumoto K, Hara T, Mild T, Itami S, Katayama I, Hearing VJ.
  • Journal Title: FASEB J 22(4) Pages: 1009-1020
  • Peer Reviewed
• [Journal Article] Melanin mediated apoptosis of epidermal cells damaged by ultraviolet radiation:factors influencing the incidence of skin cancer (2008)
  • Author(s): Yamaguchi Y(Corresponding author), Beer JZ, Hearing VJ.
  • Journal Title: Arch Dermatol Res 300(Supplement 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(Co-first and Corresponding author), Nakamura M, Kojima R, Shima R, Furui Y, Watanabe S, Takeuchi A, Kaneko N, Shintani Y, Maeda A, Tani M, Morita A, Katayama I.
  • Journal Title: J Dermatol Sci 50(3) Pages: 243-247
  • Peer Reviewed
• [Journal Article] Cyclobutane pyrimidine dimer formation and p53 production in human skin after repeated UV exposure (2008)
  • Author(s): Yamaguchi Y, Coelho SG, Zmudzka BZ, Takahashi K, Beer JZ, Hearing VJ, Miller SA.
  • Journal Title: Exp Dermatol Pages: 23
  • 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 BZ, Bushar HF, Yamaguchi Y, Hearing VJ, Beer JZ.
  • Journal Title: Br J Dermatol (In press)
  • 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 (In press)
  • Peer Reviewed
• [Journal Article] Stage III melanoma treated with chemotherapy after surgery during the second trimester of pregnancy (2008)
  • Author(s): Ishida I, Yamaguchi Y(Co-first and Corresponding author), Tanemura A, Hosokawa K, Itami S, Morita A, Katayama I.
  • Journal Title: Arch Dermatol (In press)
  • Peer Reviewed
• [Journal Article] Wounds caused by pyoderma gangrenosum and vasculopathy secondary to diabetes mellitus treated with cyclosporine and sympathectomy (2008)
  • Author(s): Takahashi Y, Yamaguchi Y(Co-first and Corresponding author), Itoh K, Sano S, Morita A, Katayama I.
  • Journal Title: Dermatol Surg (In press)
  • Peer Reviewed
• [Journal Article] Epithelioid sarcoma on the foot masquerading as an intractable wound for 24 years (2008)
  • Author(s): Nishimura Y, Yamaguchi Y(Corresponding author), Hamada K, Tomita Y, Morita A, Katayama I.
  • Journal Title: Clin Exp Dermatol (In press)
  • Peer Reviewed
• [Journal Article] Embryonic hair follicle fate alteration by augmented beta-catenin signaling relayed by Bmp receptor(BmprIA) (2008)
  • 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 (In press)
  • Peer Reviewed
• [Journal Article] Regulation of human skin pigmentation and responses to ultraviolet rad iation (2007)
  • Author(s): Miyamura Y, Coelho SG, Wolber R, Miller SA, Wakamatsu K, Z mudzka BZ, Ito S, Smuda C, Passeron T, Choi W, Batzer J, Yamaguchi Y, Beer JZ, Hearing VJ.
  • Journal Title: Pigment Cell Res 20(1) Pages: 2-13
  • Peer Reviewed
• [Journal Article] Sialylated core 1 O-glycans influence the sorting of Pme117/gp100 and determine its capacity to form fibrils (2007)
  • Author(s): Valencia JC, Rouzaud F, Julien S, Chen KG, Passeron T, Yamaguchi Y, Abu-Asab M, Tsokos M, Costin GE, Yamaguchi H, Miller Jenkins LM, Nagashima K, Appella E, Hearing VJ.
  • Journal Title: J Biol Chem 282(15) Pages: 11266-11280
  • Peer Reviewed
• [Journal Article] The effects of dickkopf 1(DKK1)on gene expression and Wnt signaling by melanocytes:mechanisms underlying its suppression of melanocyte function and proliferation (2007)
  • Author(s): Yamaguchi Y(Corresponding author), Passeron T, Watabe H, Yasumoto K, Rouzaud F, Hoashi T, Hearing VJ.
  • Journal Title: J Invest Dermatol 127(5) Pages: 1217-1225
  • Peer Reviewed
• [Journal Article] Intractable wounds caused by arteriosclerosis obliterans with end-stage renal disease treated by aggressive debridement and epidermal grafting (2007)
  • Author(s): Hanafusa T, Yamaguchi Y, Katayama I.
  • Journal Title: J Am Acad Dermatol 57(2) Pages: 322-326
  • Peer Reviewed
• [Journal Article] The regulation of skin pigmentation.[Selected as Journal Cover] (2007)
  • Author(s): Yamaguchi Y, Brenner M, Hearing VJ.
  • Journal Title: J Biol Chem 282(38) Pages: 27557-27561
  • Peer Reviewed
• [Journal Article] Intractable wounds from a herpes simplex infection in an immunosuppressed patient with rheumatoid arthritis (2007)
  • Author(s): Hanafusa T, Yamaguchi Y(Corresponding author), Kitaba S, Katayama I.
  • Journal Title: Arch Dermatol 143(10) Pages: 1340-1342
  • Peer Reviewed
• [Journal Article] Intractable wounds caused by calcific uremic arteriolopathy treated with bisphosphonates (2007)
  • Author(s): Hanafusa T, Yamaguchi Y(Corresponding author), Tani M, Umegaki N, Nishimura Y, Katayama I.
  • Journal Title: J Am Acad Dermatol 57(6) Pages: 1021-1025
  • Peer Reviewed
• [Presentation] The efficacy of epidermal grafting (2008)
  • Author(s): Yamaguchi Y
  • Organizer: World Congress of Dermatology
  • Place of Presentation: Buenos Aires,Argentine
  • Year and Date: 2008-10-03
• [Presentation] The effects of dickkopf 1 on skin pigmentation. (2008)
  • Author(s): Yamaguchi Y
  • Organizer: Avon invited lecture series
  • Place of Presentation: New York,USA
  • Year and Date: 2008-05-16
• [Presentation] The effects of dickkopf 1 on gene expression and Wnt signaling by kera tirtocvtes. (2008)
  • Author(s): Yamaguchi Y
  • Organizer: Society for Investigative dermatology
  • Place of Presentation: Los Angeles,USA
  • Year and Date: 2008-05-11
• [Presentation] The effect of DKK1 on human skin (2007)
  • Author(s): Yamaguchi Y
  • Organizer: Korean Society for Investigative Dermatology
  • Place of Presentation: Seoul,Korea
  • Year and Date: 2007-10-17
• [Presentation] The effect of DKK1 on keratinocytes (2007)
  • Author(s): Yamaguchi Y
  • Organizer: Japanese Society for Investigative Dermatology
  • Place of Presentation: Yokohama,Japan
  • Year and Date: 2007-04-20
• [Book] 1冊でわかる光皮膚科 (2008)
  • Author(s): 山口 裕史
  • Total Pages: 232
  • Publisher: 分光堂
• [Book] すぐに役立つ日常皮膚診療における私の工夫 G.ありふれた皮膚疾患のベスト治療と私の工夫 13.尋常性白斑 (2007)
  • Author(s): 山口 裕史、片山 一朗
  • Total Pages: 309
  • Publisher: 全日本病院出版会
• [Book] 皮膚科診療プラクティス 20巻 1.光皮膚科学 1)急性皮膚障害 (2007)
  • Author(s): 山口 裕史、森田 明理
  • Total Pages: 365
  • Publisher: メディカルリビュー社