Interleukin-1β-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration

Human umbilical cord Wharton's jelly derived mesenchymal stem cells (hUCMSCs), a source of cell therapy, have received a great deal of attention due to their homing or migrating ability in response to signals emanating from damaged sites. It has been found that IL-1 beta possesses the ability to induce the expression of matrix metalloproteinase-3 (MMP-3) in bone marrow MSCs. MMP-3 is involved in cell migration in various types of cells, including glioblastoma, vascular smooth muscle, and adult neural progenitor cells. In this study, we proposed that IL-1 beta influences hUCMSCs migration involving MMP-3. The expression level of MMP-3 in IL-1 beta -induced hUCMSCs was verified using cDNA microarray analysis, quantitative real-time PCR, ELISA and Western blot. Wound-healing and trans-well assay were used to investigate the cell migration and invasion ability of IL-1 beta -treated hUCMSCs. In addition, we pre-treated hUCMSCs with interleukin-1 receptor antagonist, MMP-3 inhibitors (ALX-260-165, UK 356618), or transfected with MMP-3 siRNA to confirm the role of MMP3 in IL-1 beta -induced cell migration. Our results showed that IL-1 beta induced MMP-3 expression is related to the migration of hUCMSCs. Moreover, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126, p38 inhibitor SB205380, JNK inhibitor SP600125 and Akt inhibitor GSK 690693 decreased IL-1 beta -induced MMP-3 mRNA and protein expression. The migration and invasion ability analyses showed that these inhibitors attenuated the IL-1 beta -induced migration and invasion ability of hUCMSCs. In conclusion, we have found that IL-1 beta induces the expression of MMP-3 through ERK1/2, JNK, p38 MAPK and Akt signaling pathways to enhance the migration of hUCMSCs. These results provide further understanding of the mechanisms in IL-1 beta -induced hUCMSCs migration to injury sites.

Automated summary

Human umbilical cord Wharton's jelly derived mesenchymal stem cells (hUCMSCs) have the ability to migrate to damaged sites in response to signals. IL-1 beta induces the expression of MMP-3 in hUCMSCs, which is related to cell migration. Additionally, ERK1/2, JNK, p38 MAPK and Akt signaling pathways are involved in IL-1 beta-induced hUCMSCs migration through MMP-3 expression.