NFKB1-mediated downregulation of microRNA-106a promotes oxidative stress injury and insulin resistance in mice with gestational hypertension.

This study intended to investigate the role of NFKB1 in oxidative stress injury and insulin resistance in gestational hypertension (GH) mice. Following establishment of a GH mouse model by high-fat diet, NFKB1, miR-106a, and FLOT2 expression was detected in liver of mice. After NFKB1, miR-106a, and FLOT2 were altered in GH mice by lentiviral vector, oxidative stress markers in liver tissues were examined by colorimetry, and insulin resistance was assessed by fasting blood glucose and fasting insulin levels. Next, hepatocytes were isolated from GH mice and treated with miR-106a mimic, inhibitor or siRNA, followed by determination of hepatocyte apoptosis and the expression of inflammation- and apoptosis-related factors. Evaluation of the correlations among NFKB1, miR-106a, and FLOT2 were conducted. Liver of GH mice harbored NFKB1 and FLOT2 upregulation and miR-106a downregulation. miR-106a was transcriptionally inhibited by NFKB1, and negatively targeted FLOT2. Oxidative stress injury and insulin resistance in GH mice and apoptosis and inflammation of hepatocytes from GH mice were decreased after silencing NFKB1 or FLOT2 or overexpressing miR-106a. These findings provided evidence demonstrating the inhibitory effect of NFKB1 silencing on oxidative stress injury and insulin resistance in GH mice via miR-106a upregulation and FLOT2 downregulation.