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2013 Fiscal Year Final Research Report

Biochemical process of membrane-associated protein is induced by inflammatory cytokines in cultured lymphatic endothelial cells

Research Project

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Project/Area Number 23390283
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

HIRAKAWA Satoshi  浜松医科大学, 医学部, 准教授 (50419511)

Co-Investigator(Renkei-kenkyūsha) HIGASHIYAMA Shigeki  愛媛大学, プロテオ医学研究センター, 教授 (60202272)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords増殖因子 / リンパ管新生 / 細胞内シグナル伝達
Research Abstract

The present study demonstrated that inflammatory cytokines induces the ectodomain shedding of type I transmembrane proteins in cultured human lymphatic endothelial cells. ADAM17 is responsible for the shedding via the activation of MAP kinase pathway in response to vascular endothelial factor (VEGF)-A. Furthermore, the entodomain shedding of membrane-associated protein enhanced the migration of cultured lymphatic endothelial cells in response to VEGF-A. Moreover, double immunofluorescence analysis revealed that the targeted overexpression of VEGF-A promoted the ectodomain shedding of the membrane associated protein cutaneous lymphatic vessels. Therefore, these results indicate, for the first time, that lymphangiogensis is mediated by the biochemical process of membrane-binding proteins in lymphatic endothelial cells in vitro and in vivo.

  • Research Products

    (27 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (12 results) Presentation (10 results) (of which Invited: 1 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] accelerates carcinogenesis by activating chronic inflammation and oxidative stress2014

    • Author(s)
      Aoi J, Endo M, Kadomatsu T, Miyata K, Ogata A, Horiguchi H, Odagiri H, Masuda T, Fukushima S, Jinnin M, Hirakawa S, Sawa T, Akaike T, Ihn H, Oike Y
    • Journal Title

      Mol Cancer Res

      Volume: 12 Pages: 239-49

  • [Journal Article] Lymphangiogenesis and angiogenesis in abdominal aortic aneurysm2014

    • Author(s)
      Sano M, Sasaki T, Hirakawa S, Sakabe J, Ogawa M, Baba S, Zaima N, T anaka H, Inuzuka K, Y amamoto N, Setou M, Sato K, Konno H, Unno N
    • Journal Title

      PLoS ONE

      Volume: 20;9(3) Pages: e89830

  • [Journal Article] Serum interleukin-22 and vascular endothelial growth factor serve as sensitive biomarkers but not as predictors of therapeutic response to biologics in patients with psoriasis2013

    • Author(s)
      Shimauchi T, Hirakawa S, Suzuki T, Yasuma A, Majima Y, Tatsuno K, Yagi H, Ito T, Tokura Y
    • Journal Title

      J Dermatol

      Volume: 40 Pages: 805-12

  • [Journal Article] High frequencies of positive nickel/cobalt patch tests and high sweat nickel concentration in patients with intrinsic atopic dermatitis2013

    • Author(s)
      Yamaguchi H, Kabashima-Kubo R, Bito T, Sakabe J-I, Shimauchi T, Ito T, Hirakawa S, Hirasawa N, Ogasawara K, T okura Y
    • Journal Title

      J Dermatol Sci

      Volume: 72 Pages: 240-5

  • [Journal Article] Kallikrein-related Peptidase 5 Functions in Proteolytic Processing of Profilaggrin in Cultured Human Keratinocytes2013

    • Author(s)
      Sakabe J, Y amamoto M, Hirakawa S, Motoyama A, Ohta I, T atsuno K, Ito T, Kabashima K, Hibino T, T okura Y
    • Journal Title

      J Biol Chem

      Volume: 14;288 Pages: 17179-89

  • [Journal Article] Kallikrein-related Peptidase 5 Functions in Proteolytic Processing of Profilaggrin in Cultured Human Keratinocytes2013

    • Author(s)
      Sakabe J, Y amamoto M, Hirakawa S, Motoyama A, Ohta I, Tatsuno K, Ito T, Kabashima K, Hibino T, T okura Y
    • Journal Title

      J Biol Chem

      Volume: 14;288(24) Pages: 17179-89

  • [Journal Article] Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis2012

    • Author(s)
      Asai J, Takenaka H, Hirakawa S, Sakabe J, Hagura A, Kishimoto S, Maruyama K, Kajiya K, Kinoshita S, T okura Y, Katoh N
    • Journal Title

      Am J Pathol

      Volume: 181(6) Pages: 2217-24

  • [Journal Article] Induced lymphatic sinus hyperplasia in sentinel lymph nodes by VEGF-C as the earliest premetastatic indicator2012

    • Author(s)
      Liersch R, Hirakawa S, Berdel WE, Mesters RM, Detmar M
    • Journal Title

      Int J Oncol

      Volume: 41(6) Pages: 2073-8

  • [Journal Article] A palmtop-sized microfluidic cell culture system driven by a miniaturized infusion pump2012

    • Author(s)
      Sasaki N, Shinjo M, Hirakawa S, Nishinaka M, Tanaka Y, Mawatari K, Kitamori T, Sato K
    • Journal Title

      Electrophoresis

      Volume: 33 Pages: 1729-1735

  • [Journal Article] Targeted overexpression of Angptl6/angiopoietin-related growth factor in the skin promotes angiogenesis and lymphatic vessel enlargement in response to ultraviolet B2012

    • Author(s)
      Okazaki H, Hirakawa S, Shudou M, Nakaoka Y, Shirakata Y, Miyata K, Oike Y, Hashimoto K, Sayama K
    • Journal Title

      J Dermatol

      Volume: 39 Pages: 366-74

  • [Journal Article] Angiopoietin-like protein 2 is an important facilitator of inflammatory carcinogenesis and metastasis2011

    • Author(s)
      Aoi J, Endo M, Kadomatsu T, Miyata K, Nakano M, Horiguchi H, Ogata A, Odagiri H, Y ano M, Araki K, Jinnin M, Ito T, Hirakawa S, Ihn H, Oike Y
    • Journal Title

      Cancer Res

      Volume: 71 Pages: 7502-12

  • [Journal Article] Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse2011

    • Author(s)
      Kerjaschki D, Bago-Horvath Z, Rudas M, Sexl V, Schneckenleithner C, Wolbank S, Bartel G, Krieger S, Kalt R, Hantusch B, Keller T, Nagy-Bojarszky K, Huttary N, Raab I, Lackner K, Krautgasser K, Schachner H, Kaserer K, Rezar S, Madlener S, Vonach C, Davidovits A, Nosaka H, Hämmerle M, Viola K, Dolznig H, Schreiber M, Nader A, Mikulits W, Gnant M, Hirakawa S, Detmar M, Alitalo K, Nijman S, Offner F, Maier TJ, Steinhilber D, Krupitza G
    • Journal Title

      J Clin Invest

      Volume: 121 Pages: 2000-12

  • [Presentation] Nanophysiology to better understand the function of the vasculature in health and skin disease2014

    • Author(s)
      Hirakawa S
    • Organizer
      The 24th Annual Meeting of The Korean Society for Investigative Dermatology
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      20140328-29
  • [Presentation] 皮膚と循環 : 血管・リンパ管から考える病態生理2013

    • Author(s)
      平川聡史
    • Organizer
      第90回日本生理学会大会. シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      20130327-29
  • [Presentation] A functional role of L YVE-1 in VEGF-A-induced lymphangiogenesis and psoriasis2012

    • Author(s)
      Hirakawa S
    • Organizer
      The 61st annual Montania Symposium
    • Place of Presentation
      Gleneden Beach, Oregon
    • Year and Date
      20121011-15
  • [Presentation] Biological importance of nodal lymphangiogenesis in tumor metastasis2012

    • Author(s)
      Hirakawa S
    • Organizer
      Workshop Classic and Modern in Angiogenesis and Lymphangiogenesis
    • Place of Presentation
      Timisoara, Romania
    • Year and Date
      20120522-23
  • [Presentation] New approaches for patho-physiological function in cutaneous lymphatic vessels2012

    • Author(s)
      平川聡史
    • Organizer
      第36回日本リンパ学会総会 シンポジウム3
    • Place of Presentation
      東京
    • Year and Date
      2012-06-30
  • [Presentation] Lymphatic vessels in inflammation and tumor metastasis2011

    • Author(s)
      Hirakawa S
    • Organizer
      EC8 Zurich 2011. 8 th International Symposium on the Biology of Endothelial cell
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      20110615-18
  • [Presentation] リンパ管新生とリンパ節転移の基礎的解析2011

    • Author(s)
      平川聡史
    • Organizer
      第35回日本リンパ学会総会 シンポジウム3 : リンパ行性癌転移
    • Place of Presentation
      東京
    • Year and Date
      2011-06-04
  • [Presentation] Pathological angiogenesis and lymphangiogenesis2011

    • Author(s)
      Hirakawa S
    • Organizer
      World Congress of Dermatology 2011
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      2011-05-24
  • [Presentation] 癌とリンパ管新生2011

    • Author(s)
      平川聡史
    • Organizer
      第100回日本病理学会総会 シンポジウム2腫瘍と間質 分子細胞組織からのアプローチ シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2011-04-28
    • Invited
  • [Presentation] VEGF-A induces the ectodomain shedding of L YVE-1 via MAPK pathway in cultured lymphatic endothelial cells2010

    • Author(s)
      平川聡史
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      20100922-24
  • [Book] 母斑, 血管腫・脈管形成異常, 山口徹, 今日の治療指針2013

    • Author(s)
      平川聡史
    • Total Pages
      1127
    • Publisher
      医学書院, 東京都
  • [Book] 紫斑, 瀧川雅浩2013

    • Author(s)
      平川聡史
    • Total Pages
      63-64
    • Publisher
      南江堂, 東京都
  • [Remarks]

    • URL

      http://www2.hama-med.ac.jp/w1b/derm/index.html

  • [Patent(Industrial Property Rights)] 分子標的薬の皮膚系細胞に対する傷害性を定量評価する方法2013

    • Inventor(s)
      山内豊彦, 青島正浩, 平川聡史
    • Industrial Property Rights Holder
      浜松ホトニクス株式会社, 浜松医科大学
    • Industrial Property Rights Type
      特願
    • Industrial Property Number
      2013-179143
    • Filing Date
      2013-08-30
  • [Patent(Industrial Property Rights)] 血管透過性亢進抑制作用の評価方法2013

    • Inventor(s)
      山内豊彦, 平川聡史, 山下 豊, 戸倉新樹
    • Industrial Property Rights Holder
      浜松ホトニクス株式会社, 浜松医科大学
    • Industrial Property Rights Type
      特願
    • Industrial Property Number
      2013-034570
    • Filing Date
      2013-02-25

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Published: 2015-06-25  

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