Development of a novel anti-inflammation effect in a Thrombomodulin as a platform type molecule

• Project/Area Number: 21390483
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Osaka Institute of Technology (2011); Kagoshima University (2009-2010)
• Principal Investigator: KAWAHARA Ko-ichi 大阪工業大学, 工学部, 教授 (10381170)
• Co-Investigator(Kenkyū-buntansha): MARUYAMA Ikuro 鹿児島大学, 大学院・医歯学総合研究科, 特任教授 (20082282) ; HASHIGUCHI Teruto 鹿児島大学, 大学院・医歯学総合研究科, 教授 (70250917) ; ITO Takashi 鹿児島大学, 大学院・医歯学総合研究科, 特任講師 (20381171) ; SHIMIZU Toshiaki 鹿児島大学, 医学部・歯学部・附属病院, 医員 (50468055)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2010: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 集中治療医学 / トロンボモジュリン / 炎症 / ヒストン / プラットフォーム分子 / thrombomodulin / 補体

Research Abstract

Thrombomodulin(TM) is an endothelial cell surface membrane protein and contains a large extracellular region that harbors a thrombin-binding site. TM is also expressed in other tissues, suggesting that it is thought to perform various functions. Indeed, TM, which is bound to thrombin, plays an important role in the attenuation of the inflammatory response in settings such as High mobility group box-1 protein(HMGB1) degradation. The aims of present study are whether the novel TM-binding protein exists. This study demonstrates that TM might bind to HistonH3.

Research Products

• [Journal Article] Immunohistochemical expression of thrombomodulin in vestibular schwannoma (2012)
  • Author(s): Yamahata H, Yunoue S, Tokimura H, Hanaya R, Hirano H, Tokudome M, Karki P, Yonezawa H, Sugata S, Kawahara KI, Maruyama I, Arita K
  • Journal Title: Brain Tumor Pathol Volume: (in press)
  • Peer Reviewed
• [Journal Article] MK615, a Prunus mume Steb. Et Zucc('Ume') Extract, Attenuates the Growth of A375 Melanoma Cells by Inhibiting the ERK1/2-Id-1 Pathway (2012)
  • Author(s): Tada KI, Kawahara KI, Matsushita S
  • Journal Title: Phytotherapy Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] Granulocyte and monocyte adsorption apheresis as an effective treatment for Reiter disease (2012)
  • Author(s): Yoshifuku A, Oyama K, Ibusuki A, Kawasaki M, Sakanoue M, Matsushita S, Kawai K, Kawahara K, Maruyama I, Kanekura T
  • Journal Title: Clin Exp Dermatol Volume: 37 Pages: 241-4
  • Peer Reviewed
• [Journal Article] MK615, a Prunus mume Steb.Et Zucc ('Ume') Extract, Attenuates the Growth of A375 Melanoma Cells by Inhibiting the ERK1/2-Id-1 Pathway (2012)
  • Author(s): 川原幸一
  • Journal Title: Phytotherapy Research Volume: (in press)(未定)
  • Peer Reviewed
• [Journal Article] Valproic acid increases susceptibility to endotoxin shock through enhanced release of 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 Volume: 36 Pages: 494-500
  • Peer Reviewed
• [Journal Article] NSAIDs inhibit neovascularization of chroid through HO-1-dpendency pathway (2011)
  • Author(s): Yoshinaga N, Arimura N, Otsuka H, Kawahara K, Hashiguchi T, Maruyama I
  • Journal Title: Sakamoto T. Lab Invest Volume: 91 Pages: 1277-90
  • Peer Reviewed
• [Journal Article] Edaravone : a new therapeutic approach for the treatment of acute stroke (2010)
  • Author(s): Kikuchi K, Kawahara K, Miyagi N, Uchikado H, Kuramoto T, Morimoto Y, Tancharoen S, Miura N, Takenouchi K, Oyama Y, Shrestha B, Matsuda F, Yoshida Y, Arimura S, Mera K, Tada K, Yoshinaga N, Maenosono R, Ohno Y, Hashiguchi T, Maruyama I, Shigemori M
  • Journal Title: Med Hypotheses Volume: 75 Pages: 583-5
  • Peer Reviewed
• [Journal Article] Green tea extract supplement inhibition of HMGB1 release in rats exposed to cigarette smoke (2010)
  • Author(s): Saiwichai T, Sangalangkarn V, Kawahara K, Oyama Y, Chaichalotornkul S, Narkpinit S, Harnyuttanakorn P, Singhasivanon P, Maruyama I, Tancharoen S
  • Journal Title: Southeast Asian J Trop Med Public Health Volume: 41 Pages: 250-8
  • Peer Reviewed
• [Journal Article] B Cell-Derived Vascular Endothelial Growth Factor A Promotes Lymphangiogenesis and High Endothelial Venule Expansion in Lymph Nodes (2010)
  • Author(s): Shrestha B, Hashiguchi T, Ito T, Miura N, Takenouchi K, Oyama Y, Kawahara K, Tancharoen S, Ki-I Y, Arimura N, Yoshinaga N, Noma S, Shrestha C, Nitanda T, Kitajima S, Arimura K, Sato M, Sakamoto T, Maruyama I
  • Journal Title: J Immunol Volume: 184 Pages: 4819-26
  • Peer Reviewed
• [Journal Article] Involvement of the endocannabinoid system in periodontal healing (2010)
  • Author(s): Kozono S, Matsuyama T, Biwasa KK, Kawahara K, Nakajima Y, Yoshimoto T, Yonamine Y, Kadomatsu H, Tancharoen S, Hashiguchi T, Noguchi K, Maruyama I
  • Journal Title: Biochem Biophys Res Commun Volume: 394 Pages: 928-33
  • Peer Reviewed
• [Journal Article] High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy (2010)
  • Author(s): Oyama Y, Hashiguchi T, Taniguchi N, Tancharoen S, Uchimura T, Biswas KK, Kawahara K, Nitanda T, Umekita Y, Lotz M, Maruyama I
  • Journal Title: Lab Invest Volume: 90 Pages: 853-66
  • 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) Volume: 35 Pages: 1109-15
  • NAID: 10027252218
  • Peer Reviewed
• [Journal Article] ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB (2010)
  • Author(s): Mera K, Kawahara K, Tada K, Kawai K, Hashiguchi T, Maruyama I, Kanekura T
  • Journal Title: Biochem Biophys Res Commun Volume: 397 Pages: 350-4
  • Peer Reviewed
• [Journal Article] The diagnostic value of endothelial function as a potential sensor of fatigue in health (2010)
  • Author(s): Ohno Y, Hashiguchi T, Maenosono R, Yamashita H, Taira Y, Minowa K, Yamashita Y, Kato Y, Kawahara K, Maruyama I
  • Journal Title: Vasc Health Risk Manag Volume: 24 Pages: 135-44
  • Peer Reviewed
• [Journal Article] 1, 5-Anhydroglucitol attenuates cytokine release and protects mice with type 2 diabetes from inflammatory reactions (2010)
  • Author(s): Meng X, Tancharoen S, Kawahara KI, Nawa Y, Taniguchi S, Hashiguchi T, Maruyama I
  • Journal Title: Int J Immunopathol Pharmacol Volume: 23 Pages: 105-19
  • Peer Reviewed
• [Journal Article] Role of Kenae/CCDC125 in cell motility through the deregulation of RhoGTPase (2009)
  • Author(s): Araya N, Arimura H, Kawahara K, Yagishita N, Ishida J, Fujii R, Aratani S, Fujita H, Sato T, Yamano Y, Higuchi I, Osame M, Nishioka K, Fukamizu A, Arimura K, Maruyama I, Nakajima T
  • Journal Title: Int J Mol Med Volume: 24 Pages: 605-11
  • Peer Reviewed
• [Journal Article] Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4 (2009)
  • Author(s): Kikuchi K, Tancharoen S, Matsuda F, Biswas KK, Ito T, Morimoto Y, Oyama Y, Takenouchi K, Miura N, Arimura N, Nawa Y, Meng X, Shrestha B, Arimura S, Iwata M, Mera K, Sameshima H, Ohno Y, Maenosono R, Tajima Y, Uchikado H, Kuramoto T, Nakayama K, Shigemori
  • Journal Title: Biochem Biophys Res Commun Volume: 390 Pages: 1121-5
  • 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, Tancharoen S, Matsuda F, Morimoto Y, Ito T, Biswas KK, Takenouchi K, Miura N, Oyama Y, Nawa Y, Arimura N, Iwata M, Tajima Y, Kuramoto T, Nakayama K, Shigemori M, Yoshida Y, Hashiguchi T, Maruyama I
  • Journal Title: J Pharmacol Exp Ther Volume: 329 Pages: 865-74
  • Peer Reviewed
• [Journal Article] Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc (2009)
  • Author(s): Kawahara K, Hashiguchi T, Masuda K, Saniabadi AR, Kikuchi K, Tancharoen S, Ito T, Miura N, Morimoto Y, Biswas KK, Nawa Y, Meng X, Oyama Y, Takenouchi K, Shrestha B, Sameshima H, Shimizu T, Adachi T, Adachi M, Maruyama I
  • Journal Title: Int J Mol Med Volume: 23 Pages: 615-20
  • Peer Reviewed
• [Journal Article] Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells (2009)
  • Author(s): Kikuchi K, Kawahara K, Biswas KK, Ito T, Tancharoen S, Morimoto Y, Matsuda F, Oyama Y, Takenouchi K, Miura N, Arimura N, Nawa Y, Meng X, Shrestha B, Arimura S, Iwata M, Mera K, Sameshima H, Ohno Y, Maenosono R, Yoshida Y, Tajima Y, Uchikado H, Kuramoto T
  • Journal Title: Biochem Biophys Res Commun Volume: 385 Pages: 132-6
  • Peer Reviewed
• [Journal Article] MK615 attenuates Porphyromonas gingivalis lipopolysaccharide-induced pro-inflammatory cytokine release via MAPK inactivation in murine macrophage-like RAW264.7 cells (2009)
  • Author(s): Morimoto Y, Kikuchi K, Ito T, Tokuda M, Matsuyama T, Noma S, Hashiguchi T, Torii M, Maruyama I, Kawahara K
  • Journal Title: Biochem Biophys Res Commun Volume: 389 Pages: 90-94
  • Peer Reviewed
• [Journal Article] Attenuation of LPS-induced iNOS expression by 1, 5-anhydro-d-fructose (2009)
  • Author(s): Meng X, Kawahara K, Matsushita K, Nawa Y, Shrestha B, Kikuchi K, Sameshima H, Hashiguchi T, Maruyama I
  • Journal Title: Biochem Biophys Res Commun Volume: 387 Pages: 42-46
  • Peer Reviewed
• [Journal Article] Nucleophosmin may act as an alarmin : implications for severe sepsis (2009)
  • Author(s): Nawa Y, Kawahara K, Tancharoen S, Meng X, Sameshima H, Ito T, Masuda Y, Imaizumi H, Hashiguchi T, Maruyama I
  • Journal Title: J Leukoc Biol Volume: 86 Pages: 645-53
  • Peer Reviewed