Abstract
Mesenchymal stem cells (MSCs) are known for homing to sites of injury in response to signals of cellular damage. However, the mechanisms of how cytokines recruit stem cells to target tissue are still unclear. In this study, we found that the proinflammation cytokine interleukin-1β (IL-1β) promotes mesenchymal stem cell migration. The cDNA microarray data show that IL-1β induces matrix metalloproteinase-1 (MMP-1) expression. We then used quantitative real-time PCR and MMP-1 ELISA to verify the results. MMP-1 siRNA transfected MSCs, and MSC pretreatment with IL-1β inhibitor interleukin-1 receptor antagonist (IL-1RA), MMP tissue inhibitor of metalloproteinase 1 (TIMP1), tissue inhibitor of metalloproteinase 2 (TIMP2), MMP-1 inhibitor GM6001, and protease-activated receptor 1 (PAR1) inhibitor SCH79797 confirms that PAR1 protein signaling pathway leads to IL-1β-induced cell migration. In conclusion, IL-1β promotes the secretion of MMP-1, which then activates the PAR1 and G-protein-coupled signal pathways to promote mesenchymal stem cell migration.
Highlights
Umbilical cord mesenchymal stem cells possess several properties that make them of interest as a source of cells for therapeutic use [1]
Recent research has shown that inflamed and ischemic tissue may release cytokines or growth factors such as stromal cell-derived factor- (SDF-) 1α, transforming growth factor- (TGF-) β1, monocyte chemotactic protein(MCP-) 1, tumor necrosis factor- (TNF-) α, and interleukins (IL) to promote mesenchymal stem cells homing to the injured region [2, 6]
Previous studies demonstrated that inflammatory cytokines such as transforming growth factor- (TGF-) β1, tumor necrosis factor- (TNF-) α, and IL-1β increase the production of matrix metalloproteinase (MMP) in stem cells, resulting in a strong stimulation of chemotactic migration through the extracellular matrix [2, 22]
Summary
Umbilical cord mesenchymal stem cells possess several properties that make them of interest as a source of cells for therapeutic use [1]. Previous studies demonstrated that inflammatory cytokines such as transforming growth factor- (TGF-) β1, tumor necrosis factor- (TNF-) α, and IL-1β increase the production of MMPs in stem cells, resulting in a strong stimulation of chemotactic migration through the extracellular matrix [2, 22]. These findings indicate that enhancement of the homing capacity of stem cells can be achieved through the modulation of mesenchymal stem cell responses to a variety of growth factors and cytokines. We are of the opinion that IL-1β-mediated stem cell migration involves MMP-1 expression, which activates PAR1 and influences mesenchymal stem cell migration via its signaling transduction pathway
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