| Project/Area Number |
07457235
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
MIZOGUCHI Hideaki Department of Hematology, Tokyo Women's Medical College, Professor, 医学部, 教授 (70049021)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Makio Department of Hematology, Tokyo Women's Medical College, Assistant, 医学部, 助手 (00240557)
TERAMURA Masanao Department of Hematology, Tokyo Women's Medical College, Lecture, 医学部, 講師 (40188686)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Megakaryocytopoiesis / Polyploidization / Thrombopoietin / Signal transduction / Cyclin B1 / Transcription factor / c-Mplリガンド / 巨核球産生 |
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| Research Abstract |
1.We examined the Thrombopoietin (TPO) -induced tyrosine phoshorylation of intracellular proteins in a human megakaryocytic cell line, Meg-J,which proliferates in response to TPO.Several proteins including Shc, MAP kinase, Jak2 and STAT5, were tyrosine phosphorylated after stimulation with TPO.This result shows the involvement of MAP cascade and Jak-STAT pathway in TPO-induced signal transduction.
2.We found that Meg-J cells can polyploidize and partially differentiate into mature megakaryocytes when incubated with TPO and indolocarbazol compound, K-252a. In normal cell cycles, high expression of cyclin B1 in Meg-J cells was observed during G_2/M phase. In contrast, no high expression of cyclin B1 was observed during the course of K-252a and TPO-induced polyploidization of meg-J cells. This result suggests that suppression of cyclin B1 expression is related to the prosess of polyploidization in megakaryocytopoiesis.
3.We investigated the transcription factors which are responsible for K-252a and TPO-induced polyploidization and platelet glycoprotein expression of Meg-J cells. NF-E2 antisense but not sense oligos inhibited the polyploidization and expression of GPIb. This result suggests that NF-E2 is a transcription factor essential for polyploidization and differentiation of megakaryocytic cells.
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