| 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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| 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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