regulation of autophagy flux in megakaryocyte-platelet lineage

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08873
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Iwate Medical University
• Principal Investigator: Kowata Shugo 岩手医科大学, 医学部, 講師 (30418884)
• Co-Investigator(Kenkyū-buntansha): 佐々木 了政 岩手医科大学, 医学部, 助教 (40825501)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 血小板産生 / autophagy

Outline of Final Research Achievements

In our studies of mice, autophagosome-rich platelets (ARPs), which possess autophagosomes detectable by the electron microscopic assay and the cationic fluorescent dye Cyto-ID, were increased in nascent platelets and proplatelet fragments . The dynamics of the proportion of ARPs (ARPs%) parallels that of RPs%, implying that ARPs are young platelets. To determine this property in human, we measured the proportion of ARPs% in patients with thrombocytopenia, including immune thrombocytopenia(ITP). We examined 34 patients with ITP and 52 patients with other types of thrombocytopenic disorders. Among thrombocytopenic patients, ARPs% was significantly elevated only in ITP patients (P<0.01). These data suggest that enhanced autophagy of platelets is a characteristic finding in patients with ITP and shows diagnostic potential in thrombocytopenia.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、一つの巨核球（血小板産生細胞）が、数千の血小板を短時間で産生する際に、一旦ばらばらの大きさの血小板が放出されるが短時間のうちに、均一な血小板に変化している現象について、autophagy（細胞内の自食装置）が大きく関わっている事を示した。ついでこの現象を臨床検体で把握することにより、ヒトの血小板減少症において、臨床的に原因を調べる手掛かりとなりうることを示した。今後、血小板が関わる他の疾病（血栓症、脳卒中、白血病など）における、創薬（血栓予防薬や血小板数抑制薬）、検査法（血小板産生状況、血小板の未熟さや血栓傾向の程度）の理解が進む足場となる成果が得られた。