Studies on Molecular-Cellular Mechanisms of Protein C AnticoagulantPathway Crucial for Life Maintenance

2008 Fiscal Year Final Research Report

• Project/Area Number: 19390262
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Mie University
• Principal Investigator: SUZUKI Mie University, 大学院・医学系研究科, 教授 (70077808)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Tatsuya 三重県立看護大学, 看護学科, 教授 (00242959) ; OKAMOTO Takayuki 三重大学, 大学院・医学系研究科, 助教 (30378286) ; GABAZZA Esteban 三重大学, 大学院・医学系研究科, 教授 (00293770)
• Project Period (FY): 2007 – 2008
• Keywords: 血液凝固制御 / 血管内皮細胞 / プロテインC / プロテインS / C4b結合蛋白質 / プロテインCインヒビター / トロンボモジュリン / コネキシン

Research Abstract

本研究では、生命維持に重要なプロテインC凝固制御系のうち、(1) 血中Protein S(PS)の抗凝固作用発現機構、(2) Protein C inhibitor(PCI)による臓器細胞の機能制御機構、および(3) 炎症性内皮障害を制御する細胞間接着分子の同定、に関する研究を行い、感染時の血中C4BPβ の増加がPS の抗凝固作用を低下させ、PCI が臓器固有の機能を制御し、さらに、Cx32 が血管内皮の炎症を制御することを明らかにした。

Research Products

• [Journal Article] Connexin32 isexpressed in vascular endothelial cells andparticipates in gap-junction intercellular communication (2009)
  • Author(s): Okamoto T, Akiyama M, Takeda M, GabazzaEC, Hayashi T, Suzuki K
  • Journal Title: Biochem Biophys Res Commun 382 Pages: 264-268
  • Peer Reviewed
• [Journal Article] Activated proteinC prevents hepatic ischaemia-reperfusion injury in rats (2009)
  • Author(s): Kuriyama N, Isaji S, Hamada T, Kishiwada M, Ohsawa I, Usui M, Sakurai H, Tabata M, SuzukiK, Uemoto S.
  • Journal Title: Liver Int 29 Pages: 299-307
  • Peer Reviewed
• [Journal Article] The multi-functional serpin, proteinC inhibitor : beyond thrombosis and hemostasis (2008)
  • Author(s): Suzuki K
  • Journal Title: J Thromb Haemost 6 Pages: 2017-2026
  • Peer Reviewed
• [Journal Article] Regulatorymechanisms of C4b-binding protein (C4BP)α andβ expression in rat hepatocytes by lipopolysaccharide and interleukin-6specific increase of C4BPβ expression influences the plasma level ofprotein S-C4BP complex and anticoagulantactivity of protein (2008)
  • Author(s): Kishiwada M, Hayashi T, Yuasa H, Fujii K,Nishioka J, Akita N, Tanaka H, Ido M, OkamotoT, Gabazza EC, Isaji S, Suzuki K
  • Journal Title: S. J Thromb Haemost 6 Pages: 858-1867
  • Peer Reviewed
• [Journal Article] Protein C inhibitor regulates hepatocyte growth factoractivator-mediated liver regeneration in micemodel (2008)
  • Author(s): Hamada T, Kamada H, Hayashi T, Nishioka J, Gabazza EC, Isaji S, Uemoto S, Suzuki K.
  • Journal Title: Gut 57 Pages: 365-373
  • Peer Reviewed
• [Journal Article] Protein C and its inhibitor in malignancy (2007)
  • Author(s): Suzuki K, Hayashi T
  • Journal Title: Semin Thromb Hemost 33 Pages: 667-672
  • Peer Reviewed
• [Journal Article] Intracellular localizationof protein C inhibitor (PCI) and urinaryplasminogen activator in renal tubular epithelialcells from humans and human PCI genetransgenic mice (2007)
  • Author(s): Song Z, Ma N, Hayashi T, Gabazza EC, Sugimura Y, Suzuki K
  • Journal Title: Histchem Cell Biol 128 Pages: 293-300
  • Peer Reviewed
• [Journal Article] Protein C inhibitor inhibits breast cancer cell growth,metastasis and angiogenesis independently of itsprotease inhibitory activity (2007)
  • Author(s): Asanuma K, Yoshikawa T, Hayashi T, Akita N,Nakagawa N, Hamada Y, Nishioka J, Kamada H,Gabazza EC, Ido M, Uchida A, Suzuki K
  • Journal Title: Int J Cancer 121 Pages: 955-965
  • Peer Reviewed
• [Journal Article] Protein C inhibitor directly and potently inhibits activatedhepatocyte growth factor activator (2007)
  • Author(s): Hayashi T, Nishioka J, Kamada H, Hamada K,Fujii K, Naka D, Nagaike K, Uemoto S,Kobayashi T, Hattori A, Suzuki K
  • Journal Title: J Thromb Haemost 5 Pages: 1477-1485
  • Peer Reviewed
• [Journal Article] Theinteractions among protein C inhibitor,prostate-specific antigen, and the semenogelinsystem (2007)
  • Author(s): Suzuki K, Kise H, Nishioka J, Hayashi T
  • Journal Title: Semin Thromb Hemost 33 Pages: 46-52
  • Peer Reviewed
• [Presentation] Activated protein C suppresses osteoclast differentiation. 55^<th> Annual Meeting of the Orthopaedic Research Society (2009)
  • Author(s): Yoshida K, Asanuma K, Hayashi T,Okamoto T, Suzuki K. Uchida A
  • Organizer: Las Vegas
  • Place of Presentation: USA
  • Year and Date: 20090222-25
• [Presentation] 抗凝固薬の開発状況 (2008)
  • Author(s): 鈴木宏治
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 20080326-28
• [Presentation] Protein C inhibitor regulatesbreast cancer cell growth, metastasis andangiogenesis (2008)
  • Author(s): Suzuki K
  • Organizer: The 1st International Congress on Drug Design and Discovery, Dubai
  • Place of Presentation: UAE
  • Year and Date: 20080204-07
• [Presentation] メタボリックシンドロームにおける内皮機能障害-内皮機能障害による凝固亢進の分子的背景 (2007)
  • Author(s): 鈴木宏治, 林辰弥, 岡本貴行, ガバザエステバン, 武谷浩之
  • Organizer: 第39回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20070713-14
• [Book] 血栓性素因(Thrombophiia)新臨床内科学第9版(高久史麿, 尾形悦郎, 黒川清, 矢崎義雄監修) (2008)
  • Author(s): 鈴木宏治
  • Total Pages: 949-952
  • Publisher: 医学書院(東京)
• [Book] Von Willebrand病, 血栓性血小板減少性紫斑病, 血液凝固制御系の異常, 図説分子病態学4版(一瀬白帝, 鈴木宏治編) (2008)
  • Author(s): 鈴木宏治
  • Total Pages: 250-253, 262-270
  • Publisher: 中外医学社(東京)
• [Book] 血栓症の分子病態, 小動物の血液凝固機能, 血栓症・動脈硬化モデル動物作製法(鈴木宏治) (2007)
  • Author(s): 鈴木宏治
  • Total Pages: 1-11, 39-53
  • Publisher: 金芳堂(京都)
• [Remarks] 第45回ベルツ賞(ベーリンガーインゲルハイム社主催)受賞
• [Remarks] 「鈴木・三重大教授らにベルツ賞-血管内血液凝固防止薬開発に貢献」
• [Remarks] -平成20年11月20日, 読売新聞「ベルツ賞に鈴木教授-抗血栓物質を解明」
• [Remarks] -平成20年11月20日, 中日新聞「丸山・鈴木教授の論文「血栓制御」がベルツ賞」-平成20年12月19日, 科学新聞