To Elucidate the Regulation Mechanism of Hematopoietic Stem Cell's Mobility
Project/Area Number |
18K14702
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 44010:Cell biology-related
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Research Institution | Tokai University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 造血幹細胞 / 細胞運動能の制御 / PAI-1 / P300 / PKA-CREB-P300 / p300 / マウスLSK細胞 / ヒトCD34+CD38-細胞 / がん幹細胞治療 / 白血病幹細胞 / PKA-CREB-p300 / 細胞内PAI-1 / 細胞運動制御 / ニッチ |
Outline of Final Research Achievements |
Here, we provide evidence that G-CSF mobilizing agents inhibits Smad3-dependent signaling by regulating cAMP-PKA-dependent signaling pathway in Hematopoietic Stem Cells (HSCs). G-CSF induces activation of this pathway by inhibits Smad3-dependent expression of PAI-1 through an increase in phosphorylation level of CREB protein. Mechanistically, increased p-CREB competitively inhibited the p-Smad3 from binding to the p300, which ultimately resulting in a transcriptional suppression of p-Smad3-p300 transcription regulatory complex-dependent PAI-1 gene expression. Our study reveals a novel role for G-CSF in controlling TGF-β-PAI-1 signaling to recruit HSCs into the circulation, which potentially improves clinical HSC mobilization, transplantation protocols and cancer therapy.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、静止幹細胞が運動能を獲得するに至る分子的機序を解明し、その運動能制御機構を利用した再生医療の高効率化と、がん幹細胞の運動能亢進による治療高感受性化に取り組み、PAI-1阻害剤の適応拡大を可能にした。
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Report
(6 results)
Research Products
(8 results)
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[Journal Article] Inhibition of plasminogen activator inhibitor-1 attenuates against intestinal fibrosis in mice2019
Author(s)
Imai J, Yahata T, Ichikawa H, Ibrahim AA, Yazawa M, Sumiyoshi H, Inagaki Y, Matsushima M, Suzuki T, Mine T, Ando K, Miyata T, Hozumi K.
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Journal Title
Intestinal Research
Volume: 18
Issue: 2
Pages: 219-228
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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