Analysis of the molecular mechanism regulated during megakaryopoiesis and platelet function

2013 Fiscal Year Final Research Report

• Project/Area Number: 23791069
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: KOZUMA Yukinori 筑波大学, 医学医療系, 助教 (90550145)
• Project Period (FY): 2011 – 2013
• Keywords: 巨核球 / 血小板

Research Abstract

Megakaryocytes (MKs) differentiate from hematopoietic stem cells under the control of a lineage-specific cytokine, thrombopoietin (TPO). Final stage of the maturation is characterized by platelet release from the ends of long thin cytoplasmic processes called proplatelet. However, the mechanism for regulating proplatelet formation and platelet activation produced from MKs have not been completely understood. In this study, proplatelet formation and platelet function including CD62P and PS exposure were different between wild-type (WT) and CD226 knockout (KO) or calpastatin KO or p38a +/- MKs and platelets. These results suggest that CD226, calpain-calpastatin and p38 MAPK are involved in proplatelet formation and platelet function.

Research Products

• [Journal Article] C1 galt1-deficient mice exhibit thrombocytopenia due to abnormal terminal differentiation of megakaryocytes (2013)
  • Author(s): Kudo T, Sato T, Hagiwara K, Kozuma Y, Yamaguchi T, Ikehara Y, Hamada M, Matsumoto K, Ema M, Murata S, Ohkochi N, Narimatsu H, Takahashi S
  • Journal Title: Blood Volume: 122 Pages: 1649-1657
  • DOI: 10.1182/blood-2012-12-471102
  • Peer Reviewed
• [Journal Article] Human platelets promote liver regeneration with kupffer cells in SCID mice (2013)
  • Author(s): Takahashi K, Kozuma Y, Suzuki H, Tamura T, Maruyama T, Fukunaga K, Murata S, Ohkohchi N
  • Journal Title: J Surg Res Volume: 180 Pages: 62-72
  • Peer Reviewed
• [Journal Article] 巨核球造血とアポトーシス (2012)
  • Author(s): 上妻行則
  • Journal Title: 日本血栓止血学会誌 Volume: 23 Pages: 552-558
• [Presentation] Caspase-3 activation regulates platelet lifespan but it is not involved in microparticle (MP) formation and phosphatidylserine (PS) exposure (2013)
  • Author(s): Kozuma Y, Kojima H, Tashiro Y, Ninomiya H
  • Organizer: XXIV Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Amsterdam (Nethrlands)
  • Year and Date: 20130625-26
• [Presentation] 血小板におけるcaspase-3活性化の意義の検討 (2013)
  • Author(s): 上妻行則,関崎沙織,田代ゆう子,小島寛,二宮治彦
  • Organizer: 第35回日本血栓止血学会学術集会
  • Place of Presentation: 山形
  • Year and Date: 20130530-0601
• [Presentation] Human platelets promote liver regeneration with Kupffer cells in SCID mice (2012)
  • Author(s): Takahashi K, Kozuma Y, Suzuki H, Ohkihchi N
  • Organizer: The 7^<th> Tsukuba Medical Science Research Meeting
  • Place of Presentation: Tsukuba (Japan)
  • Year and Date: 20121030-1102
• [Presentation] (2012)
  • Author(s): 高橋一広,上妻行則,鈴木英紀,野渡剛之,丸山岳人,田村孝史,野崎礼次,村田聡一郎,大河内信弘
  • Organizer: 第48回日本肝臓学会
  • Place of Presentation: 金沢
  • Year and Date: 20120607-08
• [Presentation] (2012)
  • Author(s): 高橋一広,村田聡一郎,上妻行則,鈴木英紀,野渡剛之,丸山岳人,田村孝史,野崎礼次,池田直哉,川崎卓也,大河内信弘
  • Organizer: 第112回日本外科学会
  • Place of Presentation: 千葉
  • Year and Date: 20120412-14
• [Presentation] Platalet activation is negatively regulated by the molecular interaction of platelet surface CD226 with CD112 expressed on endothelial cells (2011)
  • Author(s): Kozuma Y, Ninomiya H, Shibuya K, Shibuya A, Kojima H
  • Organizer: XXIII Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Kyoto (Japan)
  • Year and Date: 20110723-28
• [Book] 若葉マーク臨床検査技師エッセンス・ノート2臨床形態検査、止血・凝固・線溶機構 (2013)
  • Author(s): 編集:山内一由、分担:上妻行則
  • Total Pages: 217(142-155)
  • Publisher: メジカルビュー社