Elucidation of the mechanisms sepsis-induced organ dysfunction syndrome in relation to protease-activated receptors(PARs)and vascular endothelial growth factor(VEGF)

• Project/Area Number: 19390456
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Hokkaido University
• Principal Investigator: GANDO Satoshi Hokkaido University, 大学院・医学研究科, 教授 (30125306)
• Co-Investigator(Kenkyū-buntansha): MAEDA Seiji 筑波大学, 人間総合科学研究所, 講師 (30282346) ; SAWAMURA Atsushi 北海道大学, 大学院・医学研究科, 助教 (00241448) ; JESMIN Subrina 国立国際医療センター研究所, 遺伝子診断治療開発研究部, 室長 (60374261) ; YAMAGUCHI Naoto 茨城県立医療大学, 保健医療学部, 教授 (40239900) ; IEKO Masahiro 北海道医療大学, 歯学部, 教授 (50250436)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2008: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2007: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: 敗血症 / 臓器不全 / PARs / VEGF

Research Abstract

Lipopolysaccharide(LPS)により発現誘導された「Protease-activated receptors(PARs)がPARs自身による凝固・炎症反応増強機序に加えて、vascular endothelial growth factor(VEGF)の発現誘導あるいはVEGF発現抑制からさらなる炎症反応増強とアポトーシスにより脳、肺臓、肝臓、腎臓等の敗血症性臓器不全発症に深く関わっている」、という仮説を証明した。

Research Products

• [Journal Article] Expression of 4 protease-activated receptors is associated with increased levels of TNF-alpha, tissue factor, and fibrin in the frontal cortex of endotoxemic rats (2009)
  • Author(s): ジェスミンサブリナ
  • Journal Title: Thromb Res (印刷中)
  • Peer Reviewed
• [Journal Article] Protease-activated receptor 2 (PAR2) blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates renal fibrin deposition in a rat model of acute renal failure (2009)
  • Author(s): ジェスミンサブリナ
  • Journal Title: Shock (印刷中)
  • Peer Reviewed
• [Journal Article] Differential expression,time course and distribution of 4 PARs in rats endotoxin-induced acute lung injury (2007)
  • Author(s): Jesmin S, Gando S, Zaedi S, Sakuraya F.
  • Journal Title: Inflammation 30 Pages: 14-27
  • Peer Reviewed
• [Journal Article] Differential expression, time course and distribution of 4 PARs in rats endotoxin-induced acute lung injury (2007)
  • Author(s): Jesmin S
  • Journal Title: Inflammation 30 Pages: 14-27
  • Peer Reviewed
• [Journal Article] The activation of neutrophil elastase-mediated fibrinolysis is not sufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation associated with systemic inflammation (2007)
  • Author(s): Gando S
  • Journal Title: Thromb Res 121 Pages: 67-73
  • Peer Reviewed
• [Journal Article] Protease-activated receptor 2(PAR2)blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates renal fibrin deposition in a rat model of acute renal failure
  • Author(s): Jesmin S, Gando S, Zaedi S, Prodhn SH, Sawamura A, Miyauchi T, Hiroe M, Yamaguchi N.
  • Journal Title: Shock (in press)
  • Peer Reviewed
• [Journal Article] Expression of 4 protease-activated receptors is associated with increased levels of TNF-alpha, tissue factor, and fibrin in the frontal cortex of endotoxemic rats
  • Author(s): Jesmin S, Gando S, Zaedi S, Sawamura A, Yamaguchi N.
  • Journal Title: Thromb Res (in press)
  • Peer Reviewed
• [Presentation] Time-dependent alterations of VEGF and its signaling molecules in ALI in a rat model of sepsis (2008)
  • Author(s): ジェスミンサブリナ、丸藤哲、ショヘルザエディ、山口直人、小山哲夫、澤村淳
  • Organizer: 第36回日本救急医学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-14
• [Presentation] Time-dependent alterations of VEGF and its signaling molecules in ALI in a rat model of sepsis (2008)
  • Author(s): ジェスミンサブリナ
  • Organizer: 第36回日本救急医学会総会
  • Place of Presentation: 札幌ロイトン札幌
  • Year and Date: 2008-10-14
• [Presentation] Chronological expression of ET-1 and TNF-α in acute liver injury and its amelioration by PAR2 blockade in a septic rat model (2007)
  • Author(s): ジェスミンサブリナ、菅野正寛、久保田信彦、星野弘勝、早川峰司、澤村淳、丸藤哲
  • Organizer: 第35回日本救急医学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2007-10-16
• [Presentation] PAR2 BP counteracts LPS-induced inflammation and coagulation and ameliorates glomerular fibrin deposition in a rat with ARF (2007)
  • Author(s): ジェスミンサブリナ、菅野正寛、久保田信彦、星野弘勝、早川峰司、澤村淳、丸藤哲
  • Organizer: 第35回日本救急医学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2007-10-16
• [Presentation] PAR2 BP counteracts LPS-induced inflammation and coagulation and ameliorates glomerular fibrin deposition in a rat with ARF (2007)
  • Author(s): ジェスミンサブリナ
  • Organizer: 第35回日本救急医学会総会・学術集会
  • Place of Presentation: 大阪リーガロイヤルホテル
  • Year and Date: 2007-10-16
• [Presentation] Chronological expression of ET-1 and TNF-α in acute liver injury and its amelioration by PAR2 blockade in a septic rat model (2007)
  • Author(s): ジェスミンサブリナ
  • Organizer: 第35回日本救急医学会総会・学術集会
  • Place of Presentation: 大阪リーガロイヤルホテル
  • Year and Date: 2007-10-16
• [Presentation] Protease-activated receptor 2 blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates glomenular fibrin deposition in a rat model of acute renal failure (2007)
  • Author(s): Gando S, Jesmin S, Zaedi S, Prodhan HS, Sawamura A, Miyauchi T, Yamaguchi N
  • Organizer: Sepsis 2007. An International Symposium Paris.
  • Place of Presentation: Paris
  • Year and Date: 2007-09-28
• [Presentation] Protease-activated receptor 2 blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates glomenular fibrin deposition in a rat model of acute renal failure (2007)
  • Author(s): Gando S
  • Organizer: Sepsis 2007. An International Symposium Paris
  • Place of Presentation: Institut Pasteur, Paris
  • Year and Date: 2007-09-28
• [Presentation] Effects of protease-activated receptor 2 on the upregulated levels of ET-1 and TNF-α in acute liver injury in a rat model of endotoxemia (2007)
  • Author(s): Sawamura A, Jesmin S, Zaedi S, Prodhan SH, Yamaguchi N, Goto K, Gando Jesmin S, Zaedi S, Togashi H, Sultana SN, Iwashima Y, Yamaguchi N, Hiroe M, Gando S
  • Organizer: Tenth International Conference on Endothelin
  • Place of Presentation: Bergamo Italy
  • Year and Date: 2007-09-18
• [Presentation] Effects of protease-activated receptor 2 on the upregulated levels of ET-1 and TNF-α in acute liver injury in a rat model of endotoxemia (2007)
  • Author(s): Sawamura A
  • Organizer: Tenth International Conference on Endothelin
  • Place of Presentation: Centro Congressi "Giovanni XXIII", Bergamo Italy
  • Year and Date: 2007-09-18
• [Presentation] Effects of TNF-α blocking peptide on endothelin-1 levels in lungs in endotoxemic rat model (2007)
  • Author(s): awamura A, Jesmin S, Zaedi S, Prodhan SH, Yamaguchi N, Goto K, Gando S
  • Organizer: Tenth International Conference on Endothelin
  • Place of Presentation: Bergamo Italy
  • Year and Date: 2007-09-17
• [Presentation] Effects of TNF-α blocking peptide on endothelin-1 levels in lungs in en dotoxemic rat model (2007)
  • Author(s): Sawamura A
  • Organizer: Tenth International Conference on Endothelin
  • Place of Presentation: Centro Congressi "Giovanni XXIII", Bergamo Italy
  • Year and Date: 2007-09-17
• [Remarks] Jesmin S, Zaedi S, Togashi H, Sultana SN, Iwashima Y, Yamaguchi N, Hiroe M, Gando S Time-dependent alterations of VEGF and its signaling molecules in acute lung injury in a rat model of sepsis. Time-dependent alterations of VEGF and its signaling molecules in acute lung injury in a rat model of sepsis. Stime-dependent alterations of VEGF and its signaling molecules in acute lung injury in a rat model of sepsis. Shock