Expression of JAK2/STAT3 signaling pathway in human umbilical vein endothelial cells exposed to the serum of type 2 diabetic macroangiopathy patients / 第二军医大学学报

ABSTRACT

Objective To investigate the role of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway in the pathogenesis of type 2 diabetic macroangiopathy. Methods The human umbilical vein endothelial cells (HUVECs) were incubated for 24 h with the serum of healthy volunteers, simple type 2 diabetic patients and patients with type 2 diabetic macroangiopathy. JAK2 specific inhibitor AG490 was used to block the JAK2/STAT3 signaling pathway. According to different treatments, the cells were divided into normal control group (NC group, n=30), simple diabetes mellitus group (DM group, n=30), type 2 diabetic macroangiopathy group (DV group, n=30), DM+AG490 group (DM+AG490 group, n=30) and DV+AG490 group (DV+AG490 group, n=30). Real-time quantitative PCR technique was used to detect the mRNA expression of JAK2, STAT3, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (FLT1) in each group. Western blotting analysis was used to detect the protein expression of JAK2, STAT3 and phosphorylated STAT3(p-STAT3). Results Compared with the NC group, the expression of JAK2, STAT3 mRNA and JAK2, and p-STAT3 protein were significantly up-regulated in DM and DV groups (P<0.05), and the expression of JAK2, STAT3 mRNA and JAK2, p-STAT3 protein in DV groups were significantly higher than those in DM group (P< 0.05). The expression of JAK2, STAT3 mRNA and JAK2, p-STAT3 protein in DM+AG490 group and DV+AG490 group were significantly lower than those in the DM group and DV group (P< 0.05). Compared with the NC and DM group, the expression of VEGF, FLT1 mRNA was significantly up-regulated in DV group(P<0.05). Compared with the DV group, the expression of VEGF and FLT1mRNA were significantly reduced in DV+AG490 group (P< 0.05). Conclusion JAK2/STAT3 signaling pathway may play a role in the pathogenesis of type 2 diabetic macroangiopathy.