Induction of lymphangiogenesis by membrane-binding growth factors

• Project/Area Number: 20591348
• 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: HIRAKAWA Satoshi Ehime University, 医学部附属病院, 講師 (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): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 血管新生因子 / シグナル伝達 / 転写因子 / 血管新生 / ectodomain shedding / 細胞外マトリックス / リンパ管内皮細胞 / 炎症性サイトカイン / ADAM / 癌 / 細胞制御 / 増殖因子 / 炎症 / モノクローナル抗体 / 治療

Research Abstract

The present study demonstrated that type I transmembrane proteins undergo ectodomain shedding in cultured human lymphatic endothelial cells. ADAM17 or ADAM10 is responsible for shedding via the activation of MAP kinase pathway. These results indicate that lymphangiogensis is mediated by the biochemical process of membrane-binding proteins.

Research Products

• [Journal Article] Regulation of pathological lymphangiogenesis requires factors distinct from those governing physiological lymphangiogenesis. (2011)
  • Author(s): Hirakawa S.
  • Journal Title: J Dermatol Sci. 61 Pages: 85-93
  • NAID: 10030889917
  • Peer Reviewed
• [Journal Article] Multiple lymphadenopathy as an initial sign of extramammary Paget's disease. (2011)
  • Author(s): Hirakawa S, Tanemura A, Mori H, Katayama I, Hashimoto K.
  • Journal Title: Br J Dermatol. 164 Pages: 200-203
  • Peer Reviewed
• [Journal Article] Possible association of vascular endothelial growth factor with the development of edema in drug-induced hypersensitivity syndrome. (2011)
  • Author(s): Hirakawa S, Okazaki H, Sayama K, Tohyama M, Hashimoto K.
  • Journal Title: J Dermatol. 38 Pages: 292-294
  • NAID: 10029330846
  • Peer Reviewed
• [Journal Article] Regulation of pathological lymphangiogenesis requires factors distinct from those governing physiological lymphangiogenesis (2011)
  • Author(s): Hirakawa S.
  • Journal Title: Journal of Dermatological Science Volume: 61 Pages: 85-93
  • NAID: 10030889917
  • Peer Reviewed
• [Journal Article] Possible association of vascular endothelial growth factor with the development of edema in drug-induced hypersensitivity syndrome (2011)
  • Author(s): Hirakawa, et al.
  • Journal Title: Journal of Dermatology Volume: 38 Pages: 292-294
  • NAID: 10029330846
  • Peer Reviewed
• [Journal Article] Multiple lymphadenopathy as an initial sign of extramammary Paget's disease (2011)
  • Author(s): Hirakawa, et al.
  • Journal Title: British Journal of Dermatology Volume: 164 Pages: 200-203
  • Peer Reviewed
• [Journal Article] PPARγ mediates innate immunity by regulating the 1α, 25-dihydroxyvitamin D3 induced hBD-3 and cathelicidin in human keratinocytes. (2010)
  • Author(s): Dai X, Sayama K, Tohyama M, Shirakata Y, Hanakawa Y, Tokumaru S, Yang L, Hirakawa S, Hashimoto K.
  • Journal Title: J Dermatol Sci. 60 Pages: 179-186
  • NAID: 10027841095
  • Peer Reviewed
• [Journal Article] E2 Polyubiquitin-conjugating enzyme Ubc13 in keratinocytes is essential for epidermal integrity. (2010)
  • Author(s): Sayama K, Yamamoto M, Shirakata Y, Hanakawa Y, Hirakawa S, Dai X, Tohyama M, Tokumaru S, Shin MS, Sakurai H, Akira S, Hashimoto K.
  • Journal Title: J Biol Chem. 285 Pages: 30042-30049
  • Peer Reviewed
• [Journal Article] Inflammatory mediator TAK1 regulates hair follicle morphogenesis and anagen induction shown by using keratinocyte-specific TAK1-deficient mice. (2010)
  • Author(s): Sayama K, Kajiya K, Sugawara K, Sato S, Hirakawa S, Shirakata Y, Hanakawa Y, Dai X, Ishimatsu-Tsuji Y, Metzger D, Chambon P, Akira S, Paus R, Kishimoto J, Hashimoto K.
  • Journal Title: PLoS ONE 5
  • Peer Reviewed
• [Journal Article] Living skin equivalents constructed using human amnions as a matrix. (2009)
  • Author(s): Yang L, Shirakata Y, Tokumaru S, Xiuju D, Tohyama M, Hanakawa Y, Hirakawa S, Sayama K, Hashimoto K.
  • Journal Title: J Dermatol Sci. 56 Pages: 188-195
  • NAID: 10027398843
  • Peer Reviewed
• [Journal Article] Nodal Lymphangiogenesis and Metastasis : Role of Tumor-induced Lymphatic Vessel Activation in Extramammary Paget's Disease. (2009)
  • Author(s): Hirakawa S, Detmar M, Kerjaschki D, Nagamatsu S, Matsuo K, Tanemura A, Kamata N, Higashikawa K, Okazaki H, Kameda K, Nishida-Fukuda H, Mori H, Hanakawa Y, Sayama K, Shirakata Y, Tohyama M, Tokumaru S, Katayama I, Hashimoto K.
  • Journal Title: Am J Pathol. 175 Pages: 2235-2248
  • Peer Reviewed
• [Journal Article] IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression. (2009)
  • Author(s): Tohyama M, Hanakawa Y, Shirakata Y, Dai X, Yang L, Hirakawa S, Tokumaru S, Okazaki H, Sayama K, Hashimoto K.
  • Journal Title: Eur J Immunol. 39 Pages: 2779-2288
  • Peer Reviewed
• [Journal Article] Nodal lymphangiogenesis and metastasis (2009)
  • Author(s): Hirakawa S, et al.
  • Journal Title: Am J Pathol 175 Pages: 2235-2248
  • Peer Reviewed
• [Journal Article] Plasma-membrane-anchored growth factor pro-amphiregulin binds A-type lamin and regulates global transcription. (2008)
  • Author(s): Isokane M, Hieda M, Hirakawa S, Shudou M, Nakashiro K, Hashimoto K, Hamakawa H, Higashiyama S.
  • Journal Title: J Cell Sci. 121 Pages: 3608-3618
  • Peer Reviewed
• [Journal Article] The NF-kappaB, 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: 901-909
  • Peer Reviewed
• [Journal Article] PPARγ is an important transcription factor in 1α, 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
  • NAID: 10031136036
  • Peer Reviewed
• [Presentation] VEGF-A induces the ectodomain shedding of LYVE-1 via MAPK pathway in cultured lymphatic endothelial cells (2010)
  • Author(s): 平川聡史
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] リンパ管新生:癌リンパ行性転移と皮膚炎症における役割 (2010)
  • Author(s): 平川聡史
  • Organizer: 第83回日本薬理学会年会 シンポジウム
  • Place of Presentation: 大阪
• [Presentation] VEGF-A induces the ectodomain shedding of LYVE-1 via MAPK path-Way in cultured lymphatic endothelial cells (2010)
  • Author(s): 平川聡史, 東山繁樹
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場,大阪市
• [Presentation] Lymph node lymphangiogenesis (2009)
  • Author(s): 平川聡史
  • Organizer: 7^<th> World Congress on Melanoma
  • Place of Presentation: オーストリア ウィーン
  • Year and Date: 2009-05-15
• [Presentation] Intra-nodal lymphangiogenesis : a concept reflecting metastatic spread of tumors in the lymphatic system (2009)
  • Author(s): 平川聡史
  • Organizer: 第34回日本微小循環学会年次総会 シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-02-21
• [Presentation] Functional role of tumor-associated lymphatic vessels in lymph node metastasis (2009)
  • Author(s): 平川聡史
  • Organizer: 第68回日本癌学会学術総会(口演:一般演題)
  • Place of Presentation: 横浜
• [Presentation] 皮膚疾患とリンパ管新生:病態解明を目指して (2009)
  • Author(s): 平川聡史
  • Organizer: 第33回日本リンパ学会総会 シンポジウム
  • Place of Presentation: 大阪
• [Presentation] リンパ管新生:がん組織におけるリンパ管の役割 (2009)
  • Author(s): 平川聡史、橋本公二
  • Organizer: 第25回日本DDS学会
  • Place of Presentation: 東京
• [Presentation] リンパ管新生:乳房外Paget病におけるリンパ行性転移機序 (2009)
  • Author(s): 平川聡史
  • Organizer: 第7回日本臨床腫瘍学会学術集会(口演:一般演題)
  • Place of Presentation: 名古屋
• [Book] Textbook of Dermatology (2nd ed.Bologna J et al., eds.) (2008)
  • Author(s): Detmar M, Hirakawa S. MOSBY ELSEVIER.
  • Publisher: Vascular Biology.
• [Remarks] ホームページ等 なし。