| Project/Area Number |
15K09470
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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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| Research Field |
Hematology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
KIRITO Keita 山梨大学, 大学院総合研究部, 教授 (90306150)
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| Co-Investigator(Kenkyū-buntansha) |
川島 一郎 山梨大学, 大学院総合研究部, 助教 (20622369)
三森 徹 山梨大学, 大学院総合研究部, 講師 (80377514)
野崎 由美 山梨大学, 総合研究部, 助教 (80530104)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | myelofibrosis / JAK2V617F / metformin / lysyl oxidase / PP2A / 線維化 / ERストレス / Lysyl oxidase / 骨髄増殖性腫瘍 / 糖代謝 / 活性酸素 / 低酸素 / 骨髄線維化 / 乳酸 / MCT |
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| Outline of Final Research Achievements |
In the present study, we focused our attention on the role of microenvironment and cell to cell interaction to understand the mechanisms for development of myelofibrosis in myeloproliferative neoplasms (MPN). We found that JAK2V617F-positive cell lines derived from MPN patients showed elevation of several ER stress markers including phosphorylation of eIF2-alpha, nuclear localization of ATF6 and XBP1s and upregulation of glucose response protein 78. We also confirmed elevation of Lysyl-oxidase (LOX), an enzyme that regulates the crosslinking of extracellular matrix proteins such as collagen in these cells. Treatment with metformin diminished activation of ER stress pathways and suppressed LOX levels. These results indicated that LOX levels were regulated by ER stress in MPN cells. In addition, it is suggested that metformin might be a new and attractive compounds to suppress myelofibrosis in MPN.
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