2022 Fiscal Year Final Research Report
To Elucidate the Regulation Mechanism of Hematopoietic Stem Cell's Mobility
| Project/Area Number |
18K14702
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 44010:Cell biology-related
|
|---|
| Research Institution | Tokai University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2023-03-31
|
| Keywords | 造血幹細胞 / 細胞運動能の制御 / PAI-1 / P300 / PKA-CREB-P300 |
|---|
| 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.
|
| Free Research Field |
造血幹細胞
|
| 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。
|
