Defense system by thrombin-HMGB1 axis

• Project/Area Number: 20390274
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kagoshima University
• Principal Investigator: MARUYAMA Ikuro Kagoshima University, 医歯学総合研究科, 特任教授 (20082282)
• Co-Investigator(Kenkyū-buntansha): HASHIGUCHI Teruto 鹿児島大学, 医歯学総合研究科, 准教授 (70250917) ; KAWAHARA Koichi 鹿児島大学, 医歯学総合研究科, 助教 (10381170) ; SHIMIZU Toshiaki 鹿児島大学, 医学部・歯学部附属病院, 医員 (50468055)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 循環器・高血圧 / 感染症 / 細胞・組織 / HMGB1 / DIC / 感染病 / ショック

Research Abstract

An endothelial membrane protein, Thrombomodulin(TM) converts thrombin(T) from a procoagulant protease to an anticoagulant. We found that N-terminus of TM also can bind and neutralize death mediator HMGB1. T-TM complex degrades the HMGB1 bound to TM forming des-HMGB1. HMGB1 acts as triggering factor for hemostasis, innate immune and repair at injury sites. However systemic HMGB1 acts as a mediator for DIC, shock and MOF. Thus TM and HMGB1 is form a self-defense system.

Research Products

• [Journal Article] Improvement of Blood Compatibility on Polysulfone-Polyvinylpyrrolidone Blend Films as a Model Membrane of Dialyzer by Physical Adsorption of Recombinant Soluble Human Thrombomodulin(ART-123). (2011)
  • Author(s): Omichi M, Matsusaki M, Maruyama I, Akashi M.
  • Journal Title: J Biomater Sci Polym Ed. Volume: (in press)
  • Peer Reviewed
• [Journal Article] High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy. (2010)
  • Author(s): Oyama Y, Hashiguchi T, Maruyama I, et al.
  • Journal Title: Lab Invest. 90(6) Pages: 853-866
  • Peer Reviewed
• [Journal Article] Protective effect of high-mobility group box 1 blockade on acute liver failure in rats. (2010)
  • Author(s): Takano K, Maruyama I, Kitagawa Y., et al.
  • Journal Title: Shock 34(6) Pages: 573-579
  • Peer Reviewed
• [Journal Article] Spherical sulfated cellulose adsorbs high-mobility-group box chromosomal protein 1 in vitro and in vivo. (2010)
  • Author(s): Suda K, Takeuchi H, Maruyama I, Kitagawa Y, et al.
  • Journal Title: ASAIO J. 56(3) Pages: 210-214
  • Peer Reviewed
• [Journal Article] High mobility group box 1 is upregulated after spinal cord injury and is associated with neuronal cell apoptosis. (2010)
  • Author(s): Kawabata H, Setoguchi T, Yone K, Souda M, Yoshida H, Kawahara K, Maruyama I, Komiya S.
  • Journal Title: Spine (Phila Pa 1976). 35(11) Pages: 1109-1115
  • NAID: 10027252218
  • Peer Reviewed
• [Journal Article] High-mobility group box 1 is involved in the initial events of early loss of transplanted islets in mice. (2010)
  • Author(s): Matsuoka N, Itoh T, Watarai H, Sekine-Kondo E, Nagata N, Okamoto K, Mera T, Yamamoto H, Yamada S, Maruyama I, Taniguchi M, Yasunami Y.
  • Journal Title: J Clin Invest. 120(3) Pages: 735-743
  • NAID: 120002142757
  • Peer Reviewed
• [Journal Article] Hemoperfusion with a high-mobility group box 1 adsorption column can prevent the occurrence of hepatic ischemia-reperfusion injury in rats. (2010)
  • Author(s): Yamamoto T, Ono T, Ito T, Yamanoi A, Maruyama I, Tanaka T.
  • Journal Title: Crit Care Med. 38(3) Pages: 879-885
  • Peer Reviewed
• [Journal Article] Hyperoxia suppresses excessive superoxide anion radical generation in blood, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats : laboratory study. (2010)
  • Author(s): Fujita M, Tsuruta R, Kaneko T, Otsuka Y, Kutsuna S, Izumi T, Aoki T, Shitara M, Kasaoka S, Maruyama I, Yuasa M, Maekawa T.
  • Journal Title: Shock. 34(3) Pages: 299-305
  • Peer Reviewed
• [Journal Article] Neutrophil elastase inhibitor improves survival of rats with clinically relevant sepsis. (2010)
  • Author(s): Suda K, Takeuchi H, Hagiwara T, Miyasho T, Okamoto M, Kawasako K, Yamada S, Suganuma K, Wada N, Saikawa Y, Fukunaga K, Funakoshi Y, Hashimoto S, Yokota H, Maruyama I, Ishizaka A, Kitagawa Y.
  • Journal Title: Shock. 33(5) Pages: 526-531
  • Peer Reviewed
• [Journal Article] Hyperglycemia enhances excessive superoxide anion radical generation, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats. (2010)
  • Author(s): Tsuruta R, Fujita M, Ono T, Koda Y, Koga Y, Yamamoto T, Nanba M, Shitara M, Kasaoka S, Maruyama I, Yuasa M, Maekawa T.
  • Journal Title: Brain Res. 1309 Pages: 155-163
  • Peer Reviewed
• [Journal Article] Protective effect of high mobility group box 1 blockade on acute liver failure in rats. (2010)
  • Author(s): Takano K, Maruyama I, Kitagawa Y, et al.
  • Journal Title: Shock Volume: 34(6) Pages: 573-579
  • Peer Reviewed
• [Journal Article] Spherical sulfated cellulose adsorbs high-mobility-group box chromosomal protein 1 in vitro and in vivo. (2010)
  • Author(s): Suda K, Takeuchi H, Maruyama I, Kitagawa Y, et al.
  • Journal Title: ASAIO J. Volume: 56(3) Pages: 210-214
  • Peer Reviewed
• [Journal Article] High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy (2010)
  • Author(s): Oyama Y, Hashiguchi T, Maruyama I, et al.
  • Journal Title: Lab Invest (in press)
  • Peer Reviewed
• [Journal Article] Minocycline attenuates both OGD-induced HMGB1 release and HMGBlinduced cell death in ischemic neuronal injury in PC12 cells. (2009)
  • Author(s): Kikuchi K, Kawahara K, Hashiguchi T, Maruyama I, et al.
  • Journal Title: Biochem Biophys Res Commun. 385(2) Pages: 132-136
  • Peer Reviewed
• [Journal Article] The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells. (2009)
  • Author(s): Kikuchi K, Kawahara K, Hashiguchi T, Maruyama I, et al.
  • Journal Title: J Pharmacol Exp Ther. 329(3) Pages: 865-874
  • Peer Reviewed
• [Journal Article] Xanthine oxidase is one of the major sources of superoxide anion radicals in blood after reperfusion in rats with forebrain ischemia/reperfusion. (2009)
  • Author(s): Ono T, Tsuruta R, Fujita M, Aki HS, Kutsuna S, Kawamura Y, Wakatsuki J, Aoki T, Kobayashi C, Kasaoka S, Maruyama I, Yuasa M, Maekawa T.
  • Journal Title: Brain Res. 1305 Pages: 158-167
  • NAID: 120002220601
  • Peer Reviewed
• [Journal Article] High-mobility group box 1 protein in CSF of patients with subarachnoid hemorrhage. (2009)
  • Author(s): Nakahara T, Tsuruta R, Kaneko T, Yamashita S, Fujita M, Kasaoka S, Hashiguchi T, Suzuki M, Maruyama I, Maekawa T.
  • Journal Title: Neurocrit Care. 11(3) Pages: 362-368
  • Peer Reviewed
• [Journal Article] Elevation of jugular venous superoxide anion radical is associated with early inflammation, oxidative stress, and endothelial injury in forebrain ischemia-reperfusion rats. (2009)
  • Author(s): Aki HS, Fujita M, Yamashita S, Fujimoto K, Kumagai K, Tsuruta R, Kasaoka S, Aoki T, Nanba M, Murata H, Yuasa M, Maruyama I, Maekawa T.
  • Journal Title: Brain Res. 1292 Pages: 180-190
  • Peer Reviewed
• [Journal Article] An elevated value of high mobility group box 1 is a potential marker for poor response to high-dose of intravenous immunoglobulin treatment in patients with Kawasaki syndrome. (2009)
  • Author(s): Eguchi T, Nomura Y, Hashiguchi T, Masuda K, Arata M, Hazeki D, Ueno K, Nishi J, Kawano Y, Maruyama I.
  • Journal Title: Pediatr Infect Dis J. 28(4) Pages: 339-341
  • Peer Reviewed
• [Journal Article] Minocycline attenuates both OGD-induced HMGB1 release and HMGB1induced cell death in ischemic neuronal injury in PC12 cells.- (2009)
  • Author(s): Kikuchi K, Kawahara K, Hashiguchi T, Maruyama I, et al.
  • Journal Title: Biochem Biophys Res Commun. 385(2) Pages: 132-6
  • Peer Reviewed
• [Journal Article] The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells (2009)
  • Author(s): Kikuchi K, Kawahara K, Hashiguchi T, Maruyama I, et al.
  • Journal Title: J Pharmacol Exp Ther. 329(3) Pages: 865-74
  • Peer Reviewed
• [Journal Article] Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells. (2008)
  • Author(s): Kawahara K, Hashiguchi T, Maruyama I, et al.
  • Journal Title: Int J Mol Med. 22(5) Pages: 639-644
  • Peer Reviewed
• [Journal Article] Proteolytic cleavage of high mobility group box 1 protein by thrombin-thrombomodulin complexes. (2008)
  • Author(s): Ito T, Kawahara K, Maruyama I, et al.
  • Journal Title: Biochem Biophys Res Commun. 377(2) Pages: 642-647
  • Peer Reviewed
• [Journal Article] Proteolytic cleavage of high mobility group box 1 protein by thrombin-thrombomodulin complexes. (2008)
  • Author(s): Ito T, Kawahara K, Maruyama I, et al.
  • Journal Title: Arterioscler Thromb Vasc Biol. 28(10) Pages: 1825-1830
  • Peer Reviewed
• [Journal Article] Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells. (2008)
  • Author(s): Kawahara K, Hashiguchi T, Maruyama I, and, et al.
  • Journal Title: Int J Mol Med. 22(5) Pages: 639-44
  • Peer Reviewed
• [Journal Article] Proteolytic cleavage of high mobility group box 1 protein by thrombin-thrombomodulin complexes. (2008)
  • Author(s): Ito T, Kawahara K, Maruyama I, and, et al.
  • Journal Title: Arterioscler Thromb Vase Biol. 28(10) Pages: 1825-30
  • Peer Reviewed
• [Presentation] Therapeutic strategy for circulating "bad" HMGB1 in septic shock. (2009)
  • Author(s): Maruyama I.
  • Organizer: 第2回HMGB1会議
  • Place of Presentation: ハンブルグ(ドイツ)
  • Year and Date: 2009-09-25
• [Presentation] Therapeutic strategy for circulating "bad" HMGB1 in septic shock (2009)
  • Author(s): Maruyama I
  • Organizer: 第2回HMGB1会議
  • Place of Presentation: ハンブルグ(ドイツ)
  • Year and Date: 2009-09-25