regulation of autophagy flux in megakaryocyte-platelet lineage
| Project/Area Number |
19K08873
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
Kowata Shugo 岩手医科大学, 医学部, 講師 (30418884)
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| Co-Investigator(Kenkyū-buntansha) |
佐々木 了政 岩手医科大学, 医学部, 助教 (40825501)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 血小板産生 / autophagy / 血小板 / 巨核球 / JAK2遺伝子変異 / PDL-1 / proplatelet / thrombopoiesis / mitchondria / Autophagy / platelet production |
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| Outline of Research at the Start |
血小板は止血機能に重要な細胞です。一方血小板は脳梗塞や心筋梗塞を生じる引き金の一つでもあることも解っています。通常、骨髄で産生された血小板は血液中で7日間働いたのちに寿命を終えます。今回の研究は、血小板が生まれ寿命を終えるまでに、autophagyが血小板内でどのような働きをしているかを研究します。その結果、血小板が関連する特定の病気を見つける検査法や、治療の手がかりを掴むことが期待されます。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Acute Liver Injury Due to T-cell Infiltration into the Liver as an Initial Clinical Finding of Adult T-cell Leukemia/Lymphoma2021
Author(s)
Keisuke,Kakisaka.,Yuji,Suzuki.,Shugo,Kowata.,Shigeki,Ito.,Yasuhiro,Takikawa.
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Journal Title
Internal Medicine
Volume: 60
Issue: 15
Pages: 2431-2436
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2021-08-01
Related Report
Peer Reviewed
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[Journal Article] Autophagosome-rich Platelets are increased in immune thrombocytopenia.2020
Author(s)
Akihiro,Otsu.,Shugo,Kowata.,Yuki,Seki.,Kazunori,Murai.,Kazuki,Kiyohara.,Shinri,Miyajima.,Wataru,Izumita.,Jiro,Hitomi.,Yoji,Ishida.,Shigeki,Ito.
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Journal Title
Journal of Iwate Medical Association
Volume: 72
Pages: 103-113
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Treatment-free remission after ffirst-line dasatinib discontinuation in patients with chronic myeloid leukaemia2020
Author(s)
Kimura S, Imagawa J, Murai K, Hino M, Kitawaki T, Okada M, Tanaka H, Shindo M, Kumagai T, Ikezoe T, Uoshima N, Sato T, Watanabe R, Kowata S, Hayakawa M, Hosoki T, Ikeda K
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Journal Title
Lancet Haematol.
Volume: 7
Pages: 218-225
Related Report
Peer Reviewed
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[Journal Article] Doripenem versus meropenem as first-line empiric therapy of febrile neutropenia in patients with acute leukemia: a prospective, randomized study.2020
Author(s)
Oyake T, Takemasa-Fujisawa Y, Sugawara N, Mine T, Tsukushi Y, Hanamura I, Fujishima Y, Aoki Y, Kowata S, Ito S, Ishida Y.：
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Journal Title
Ann. Hematol
Volume: 98
Pages: 1209-1216
Related Report
Peer Reviewed
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