Activating α7nAChRs enhances endothelial progenitor cell function partially through the JAK2/STAT3 signaling pathway

Microvascular injury is a common pathological process in ischemia-reperfusion injury. Endothelial progenitor cells (EPCs) are vital cells for angiogenesis and endothelial repair. These cells can home to injury sites and secrete angiogenic growth factors. α7nAChRs are pivotal in cholinergic angiogenesis, which is associated with endothelial cells and EPCs. Our study was designed to determine whether activating α7nAChRs enhances the function of EPCs and to explore the underlying mechanism. EPCs were derived from the bone marrow of male Sprague-Dawley rats and treated with an α7nAChR agonist (PNU282987), an α7nAChR antagonist (MLA) and a JAK2 antagonist (AG490). We then assayed the angiogenic abilities of the EPCs, including proliferation ability, adhesion ability, migration ability and in vitro tube formation ability. The levels of total JAK2 (t-JAK2), phosphorylated JAK2 (p-JAK2), total STAT3 (t-STAT3) and phosphorylated STAT3 (p-STAT3) were estimated by western blot analysis. PNU282987 treatment facilitated the angiogenic abilities of EPCs compared with the control regimen. The western blot data suggested that PNU282987 increased the levels of p-JAK2 and p-STAT3. However, the differences in t-JAK2 levels and t-STAT3 levels between the agonist-treated group and the control group were not significant. Moreover, treating EPCs with AG490 reduced STAT3 phosphorylation and attenuated the PNU282987-induced enhancement of EPCs. We demonstrated that activating α7nAChRs can enhance EPC functions partially through the JAK2/STAT3 signaling pathway. This study reveals that α7nAChRs are potential therapeutic targets for angiogenesis and that the JAK2/STAT3 pathway plays a vital role in the associated therapeutic mechanism. •PNU282987 can enhance the proliferation, adhesion, migration and tube formation abilities of EPCs.•PNU282987 promotes EPC functions partially through the JAK2/STAT3 signaling pathway.•AG490 can attenuate the beneficial effects of PNU282987 on EPCs.