| 研究実績の概要 |
Tissue plasminogen activator (tPA), aside from its vascular fibrinolytic action, exerts various effects within the body, ranging from synaptic plasticity to control of cell fate.
The purpose of this study was to investigate the mechansim of action of fibrinolytic factors on bone marrow(BM) mesenchymal(MSC) proliferation and their capactiy to support hematopoiesis. This year we were able to showed that by activating plasminogen and matrix metalloprotenase-9, tPA expands murine bone marrow-derived CD45(-)TER119(-)Sca-1(+)PDGFRα(+) mesenchymalstromal cells (PαS-MSCs) in vivo through a crosstalk between PαS-MSCs and endothelial cells. Mechanistically, tPA induces the release of Kit ligand from PαS-MSCs, which activates c-kit(+) endothelial cells to secrete MSC growth factors: platelet-derived growth factor-BB(PDGF-BB) and fibroblast growth factor 2(FGF2). In synergy, FGF2 and PDGF-BB upregulate PDGFRα expression in PαS-MSCs, which ultimately leads to PαS-MSCs expansion. These data show a novel mechanism by which the fibrinolytic system expands PαS-MSCs through a cytokine crosstalk between niche cells.
These results were published: Dahri et al. Blood Blood 2016 128:1063-1075.
The remaining year, we are studying in more detail how this mechanism might influence other cell type in the BM microenvironment.
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