Establishment and dynamism of des-HMGB1, degraded HMGB1 by thrombin-thrombomodulin

2011 Fiscal Year Final Research Report

• Project/Area Number: 23659491
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kagoshima University
• Principal Investigator: MARUYAMA Ikuro 鹿児島大学, 医歯学総合研究科, 特任教授 (20082282)
• Co-Investigator(Kenkyū-buntansha): KAWAHARA Koichi (10381170) ; HASHIGUCHI Teruto (70250917) ; OYAMA Yoko (20583470) ; ITO Takashi (20381171)
• Project Period (FY): 2011
• Keywords: 血栓 / 止血学

Research Abstract

We previously showed that HMGB1 binds to thrombomodulin(TM) and degraded by thrombin-TM at the N-terminus of the molecule cleaving out 10 aminoacdid-residue. We named this degraded HMGB1 as des-HMGB1. We also have showed that des-HMGB1 compete with intact binding to its receptor RAGE, Toll-like receptor-2 and-4 resulting negatively regulating of intact HMGB1 and its receptor signaling.
In this study, we established the des-HMGB1 specific assay ELISA, and investigated its dynamism in various diseases including DIC, sepsis and shock. We showed that the des-HMGB1 was increased in the serum from the patients with these pathologic conditions, especially in the cases treated with recombinant TM. We are now further studying relationship between des-HMGB1 levels and the efficacy of TM treatment and their prognosis.

Research Products

• [Journal Article] Role of high mobility group box chromosomal protein 1 in ischemia-reperfusion injury in the rat small intestine (2012)
  • Author(s): Kojima M, Tanabe M, Shinoda M, Yamada S, Miyasho T, Suda K, Hibi T, Obara H, Itano O, Kawachi S, Kitajima M, Maruyama I, Kitagawa Y.
  • Journal Title: J Surg Res
  • Peer Reviewed
• [Journal Article] Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction (2012)
  • Author(s): Hashimoto T, Ishii J, Kitagawa F, Yamada S, Hattori K, Okumura M, Naruse H, Motoyama S, Matsui S, Tanaka I, Izawa H, Maruyama I, Nomura M, Ozaki Y.
  • Journal Title: Atherosclerosis Volume: 221(2) Pages: 490-5
  • Peer Reviewed
• [Journal Article] Mitigation of occult lung injury by pneumonectomy via minithoracotomy in mice (2012)
  • Author(s): Kohno M, Watanabe M, Izumi Y, Tasaka S, Kitagawa Y, Maruyama I, Kobayashi K.
  • Journal Title: Thorac Cardiovasc Surg Volume: 60(2) Pages: 124-30
  • Peer Reviewed
• [Journal Article] Prediction of the neurological outcome with intrathecal high mobility group box 1 and S100B in cardiac arrest victims (2012)
  • Author(s): Oda Y, Tsuruta R, Fujita M, Kaneda K, Kawamura Y, Izumi T, Kasaoka S, Maruyama I., Maekawa T
  • Journal Title: A pilot study
  • Peer Reviewed
• [Journal Article] Thrombomodulin : protectorate God of the vasculature in thrombosis and inflammation (2011)
  • Author(s): Takashi Ito & Ikuro Maruyama.
  • Journal Title: Journal of Thrombosis and Haemostasis Volume: 9 Pages: 168-173
  • Peer Reviewed
• [Journal Article] 新規DIC治療薬トロンボモジュリン製剤の作用機序 (2011)
  • Author(s): 伊藤隆史、丸山征郎
  • Journal Title: 臨床血液 Volume: 52 Pages: 356-360
• [Journal Article] Valproic acid increases susceptibility to endotoxin shock through enhanced release o f high-mobility group box 1 (2011)
  • Author(s): Sugiura S, Ishihara Y, Komatsu T, Hagiwara M, Tanigawa N, Kato Y, Mizutani H, Kawahara K, Maruyama I, Noguchi T, Matsushita K.
  • Journal Title: Shock 2011 Volume: 36(5) Pages: 494-500
  • Peer Reviewed
• [Journal Article] Thrombomodulin : protectorate God of the vasculature in thrombosis and inflammation (2011)
  • Author(s): Ito T, Maruyama I.
  • Journal Title: J Thromb Haemost Volume: 1 Pages: 168-73
  • Peer Reviewed
• [Journal Article] Gradual increase of high mobility group protein b1 in the lungs after the onset of acute exacerbation of idiopathic pulmonary fibrosis (2011)
  • Author(s): Ebina M, Taniguchi H, Miyasho T, Yamada S, Shibata N, Ohta H, Hisata S, Ohkouchi S, Tamada T, Nishimura H, Ishizaka A, Maruyama I, Okada Y, Takashi K, Nukiwa T.
  • Journal Title: Pulm Med Volume: 2011 Pages: 916486
  • Peer Reviewed