Study on the effects of dysfunctional sphingosine 1-phosphate signal on arteriosclerosis and thrombosis

• Project/Area Number: 21790316
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Gifu Pharmaceutical University (2010-2011); Mie University (2009)
• Principal Investigator: AOKI Shinya 岐阜薬科大学, 薬学部, 助教 (10508758)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: スフィンゴシン1-リン酸 / 組織因子 / 炎症生因子 / 動脈硬化 / 血栓症 / 血栓 / 血管内皮細胞 / 赤血球 / 血小板 / LDL / HDL / アルブミン / トロンボキサンA_2 / 動脈硬化症 / 血液凝固反応 / 血栓形成 / 炎症

Research Abstract

Sphingosine 1-phosphate(Sph-1-P), abundantly stored in platelets, is released by the platelets' activation. However, the role of released Sph-1-P from activated platelets is remained unclear. In the present study, it was revealed that, in vascular endothelial cells, 1) the supernatant of the activated platelets(Plt-sup) enhanced TNF-a-induced expression of tissue factor(TF), an initiator of coagulation system, that was stimulated by Sph-1-P into the Plt-sup, 2) that Sph-1-P could enhance the expression of TF induced by inflammatory mediators, and 3) that Sph-1-P promoted TF expression by the induction of the transcriptional factors such as Egr-1, NF-kB and AP-1 through MAPK cascade. These results suggest that Sph-1-P would closely be involved in the exacerbation of arteriosclerosis and thrombosis disease.

Research Products

• [Journal Article] Inhibition of allergic bronchial asthma by thrombomodulin is mediated by dendritic cells (2011)
  • Author(s): Takagi T, Taguchi O, Toda M, Ruiz DB, Bernabe PG, D' Alessandro-Gabazza CN, Miyake Y, Kobayashi T, Aoki S, Chiba F, Yano Y, Conway EM, Munesue S, Yamamoto Y, Yamamoto H, Suzuki K, Takei Y, Morser J, Gabazza EC
  • Journal Title: American journal of respiratory and critical care medicine Volume: 183 Pages: 31-42
• [Journal Article] Inhibition of allergic bronchial asthma by thrombomodulin is mediated by dendritic cells (2011)
  • Author(s): 高木健裕
  • Journal Title: American journal of respiratory and critical care medicine Volume: 183 Issue: 1 Pages: 31-31
  • DOI: 10.1164/rccm.201001-0107oc
  • Peer Reviewed
• [Journal Article] Pulmonary hypertension is ameliorated in mice deficient in thrombin-activatable fibrinolysis inhibitor (2010)
  • Author(s): Qin L, D' Alessandro-Gabazza CN, Aoki S, Gil-Bernabe P, Yano Y, Takagi T, Boveda-Ruiz D, Ramirez Marmol AY, San Martin Montenegro VT, Toda M, Miyake Y, Taguchi O, Takei Y, Morser J, Gabazza EC
  • Journal Title: Journal of thrombosis and haemostasis Volume: 8 Pages: 808-16
• [Journal Article] Direct effects of protein S in ameliorating acute lung injury (2009)
  • Author(s): Takagi T, Taguchi O, Aoki S, Toda M, Yamaguchi A, Fujimoto H, Boveda-Ruiz D, Gil-Bernabe P, Ramirez AY, Naito M, Yano Y, D' Alessandro-Gabazza CN, Fujiwara A, Takei Y, Morser J, Gabazza EC
  • Journal Title: Journal of thrombosis and haemostasis Volume: 7 Pages: 2053-63