Effect of thioredoxin-interacting protein on Wnt/β-catenin signaling pathway and diabetic myocardial infarction

AbstractObjectiveTo explore the regulatory role of thioredoxin-interacting protein (TXNIP) in Wnt/β-catenin signaling pathway and therefore to elucidate its function in diabetic myocardial infarction.MethodsDiabetic myocardial infarction models were generated in mice. The expression levels of TXNIP and β-catenin and level of reactive oxygen species (ROS) were determined and compared with those in control group. Human umbilical vein endothelial cells were treated with high-concentration glucose and/or silencing TXNIP and/or H2O2. After 24 h, expression levels of TXNIP, β-catenin and its downstream protein Cyclin D1, and C-myc gene were determined by real-time PCR, Western blot and immunofluorescence method. The cell proliferation and ROS production capability in different groups were determined by methyl thiazolyl tetrazolium assay.ResultsCompared with control group, hyperglycemia significantly up-regulated TXNIP expression and ROS level in the myocardium and endothelial cells of myocardial infarction area, whereas the β-catenin expression was down-regulated, and the difference was statistically significant (P < 0.05). In comparison with Human umbilical vein endothelial cells in the control group, high glucose level increased the levels of TXNIP expression and ROS level in cells, but reduced cell proliferation as well as migration capability and expression levels of β-catenin, Cyclin D1 and C-myc; the difference was statistically significant (P < 0.05). However, this trend can be partially reversed by silencing TXNIP.ConclusionsDiabetic myocardial ischemia could up-regulate levels of TXNIP expression and ROS production in endothelial cells of myocardial infarction area. The regulation effect of TXNIP on β-catenin was partially achieved by changing ROS levels