Kv1.3 mediates ox-LDL-induced vascular smooth muscle cell proliferation through JAK2/STAT3 signaling pathway

Abstract

Kv1.3 channel has been shown to participate in regulating inflammatory activation, proliferation and apoptosis in several cell types. However, most of those existing studies focused on the ion-conducting properties of Kv1.3 in maintaining the resting potential and regulating Ca2+ influx. The aim of our study was to explore whether the Kv1.3-JAK2/STAT3 signaling pathway was involved in oxidized low density lipoprotein (ox-LDL) induced vascular smooth muscle cell (VSMC) proliferation. VSMCs from mouse aorta were cultured and treated with ox-LDL (25 μg/mL). The cell counting kit-8 was used to assess cell proliferation, and western blotting was performed to detect expression levels of Kv1.3, JAK2/STAT3, phosphorylated JAK2/STAT3, cyclin B1 and cyclin D1 in treated VSMCs. VSMCs were transfected with Kv1.3 small interfering RNA (Kv1.3-siRNA) or infected with a Kv1.3 lentiviral expression vector (Lv-Kv1.3) and treated with a JAK2 inhibitor LY2784544 to assess the role of Kv1.3 and JAK2/STAT3 signaling in mediating VSMC proliferation induced by ox-LDL. Ox-LDL induced cell proliferation and upregulated the expression of Kv1.3 in mouse VSMCs. In VSMCs transfected with Kv1.3-siRNA, ox-LDL was not efficient in inducing cell proliferation or the levels of proliferation associated proteins, cyclin B1 and cyclin D1. However, cell proliferation, cyclin B1 and cyclin D1 levels increased in VSMCs infected with Lv-Kv1.3. Levels of phosphorylated JAK2 and STAT3 were increased in ox-LDL-treated VSMCs, and this increase was prevented in VSMCs transfected with Kv1.3-siRNA. Treatment with the JAK2 inhibitor LY2784544 also prevented the increase in VSMCs proliferation treated with ox-LDL. Our findings demonstrated that Kv1.3 promoted proliferation of VSMCs treated with ox-LDL, and that this effect might be mediated through activation of the JAK2/STAT3 signaling pathway.