Role of microRNA-29b in interleukin-3 stimulated migration and proliferation of vascular smooth muscle cell

Abstract

Interleukin-3 (IL-3) level is especially known to increase significantly during vessel damage in the cardiovascular system and is involved in the proliferation and migration of smooth muscle cells (SMCs) through the activation of the ERK1/ERK2 MAPkinase and PI-3K/Akt pathways. MicroRNA-29b is known to regulate cell growth and target Mcl-1 and MMP2, which are highly important molecules in the proliferation and migration of cancer cells. However, the roles of microRNA-29b in other cell types still remain unknown. Therefore, we hypothesized that microRNA-29b may control SMCs that have gone through the proliferation and migration processes induced by IL-3 stimulation by inhibiting its own specific targets. In this study, IL-3 stimulated the proliferation and migration of SMCs, while microRNA-29b inhibited these effects. These findings were confirmed by a proliferation and migration assay. The expression levels or activation of Mcl-1 and MMP2, which are considered important proteins related to the IL-3-simulated signaling pathway, were also increased with IL-3 stimulation. MicroRNA-29b treatment resulted in significant reductions of Mcl-1 and MMP2 in RT-PCR and the immunoblot assay. In addition to Mcl-1 and MMP2, the upstream signal proteins stimulated by IL-3 were also investigated. IL-3 activated ERK and AKT, but microRNA-29b did not suppress the activation of these proteins. Finally, the luciferase assay showed that microRNA-29b was able to selectively downregulate Mcl-1 and MMP2 expression. This study demonstrated that microRNA-29b successfully suppressed the proliferation and migration of SMCs induced by IL-3 treatment through the inhibition of the signaling pathway related to Mcl-1 and MMP2.