Heat Shock Protein 90 Stimulates Rat Mesenchymal Stem Cell Migration via PI3K/Akt and ERK1/2 Pathways

The objective of this study was to determine the role of Hsp90 alpha in regulating the migration of mesenchymal stem cells (MSCs) and to investigate the underlying mechanisms of this effect. MSCs migration was assessed by wound healing assay and transwell migration assay. Hsp90 alpha expression was silenced in MSC by siRNA (sirHsp90 alpha). The activity of secreted metalloproteases MMP-2 and MMP-9, and their expression levels in MSC were evaluated using gelatin zymography, Western blot analysis and real-time PCR. Gene expression of VCAM-1 and CXCR4 cytokines was evaluated by real-time PCR. Akt and ERK activity were analyzed by Western blotting using antibodies against phosphorylated forms of these proteins. Treatment with Hsp90 alpha significantly enhanced MSC migration, and this effect was blocked by transfecting MSC with sirHsp90 alpha. Treating the cells with recombinant human Hsp90 alpha (rhHsp90 alpha) enhanced gene expression and protein levels of MMP-2 and MMP-9, as well as their secretion and activity. MSC incubated with rhHsp90 alpha exhibited increased gene expression of CXCR4 and VCAM-1. Finally, the levels of phosphorylated Akt and Erk were markedly increased by rhHsp90 alpha treatment. These findings indicate that Hsp90 alpha promotes MSCs migration via PI3K/Akt and ERK signaling pathways, and that this effect is possibly mediated by MMPs, SDF-1/CXCR4 pathway, and VCAM-1.