Interaction of profilin-1 and F-actin via a β-arrestin-1/JNK signaling pathway involved in prostaglandin E(2)-induced human mesenchymal stem cells migration and proliferation.

Although many previous reports have examined the function of prostaglandin E(2) (PGE(2)) in the migration and proliferation of various cell types, the role of the actin cytoskeleton in human mesenchymal stem cells (hMSCs) migration and proliferation has not been reported. The present study examined the involvement of profilin-1 (Pfn-1) and filamentous-actin (F-actin) in PGE(2)-induced hMSC migration and proliferation and its related signal pathways. PGE(2) (10(-6) M) increased both cell migration and proliferation, and also increased E-type prostaglandin receptor 2 (EP2) mRNA expression, β-arrestin-1 phosphorylation, and c-Jun N-terminal kinase (JNK) phosphorylation. Small interfering RNA (siRNA)-mediated knockdown of β-arrestin-1 and JNK (-1, -2, -3) inhibited PGE(2)-induced growth of hMSCs. PGE(2) also activated Pfn-1, which was blocked by JNK siRNA, and induced F-actin level and organization. Downregulation of Pfn-1 by siRNA decreased the level and organization of F-actin. In addition, specific siRNA for TRIO and F-actin-binding protein (TRIOBP) reduced the PGE(2)-induced increase in hMSC migration and proliferation. Together, these experimental data demonstrate that PGE(2) partially stimulates hMSCs migration and proliferation by interaction of Pfn-1 and F-actin via EP2 receptor-dependent β-arrestin-1/JNK signaling pathways.