Resistin Inhibits Glycogen Tontent In HepG2 Cells By P65/K8 Pathway

Resistin, as an important adipose tissue specificity secreted factor linking between obesity and insulin resistance, can reduce insulin sensitivity, inhibit glucose uptake stimulated by insulin. Keratin is typical intermediate filament protein in epithelial cells. As part of the epithelial cell skeleton, keratin plays an important role in maintenance of stability and integridy in the epithelial cells and tissues. And some of keratins have regulating function involved in the cell signaling pathways. More can play an important role in the clinical application as a marker in cancer diagnosis. Recent researches find that keratin 8,an important member of keratins, also play an important role in glucose metabolism. Glucose accumulation stimulated by insulin can be promoted in the normal liver cells and hepatoma cells of mice afre knockout K8/K18,but its mechanism is not clear,especially the effection of resistin on glucose metabolism mediated by keratin 8. This paper mainly studies the effection of keratin 8 on glucose metabolism in HepG2 cells and the expression of keratin 8 regulated by resistin with real-time fluorescence quantitative PCR, dual luciferase report system and chromatin immunoprecipitation methods.The results as follows:1. The results of cell tansfection and gene knockdown experement show that resistin inhibits glycogen accumulation,knockdown of keratin 8 promotes glycogen accumulation and reverses the inhibition of resistin on glycogen content in HepG2 cells.2. Bioinformatics analysis showed that, the promoter of keratin 8 has typical p65 binding element. The dual luciferase report system and ChIP experiments determine that p65 can up-regulate expression of keratin 8 by binding to specific region on the promoter of keratin 8.3. Treatment of HepG2 with different concentrations of recombinant of resistin found that,resistin can obviously inhhibit glycogen accumulation in hepatic cells and this effection is that resistin regulates transcriptional expression of keratin 8 by p65 signal pathway resulting in inhibition of glycogen accumulation in HepG2 cells.In short, Resistin can inhibit glycogen accumulation through mediating p65/K8 expression in HepG2 cells. And p65 can regulate expression of K8 by binding to the promoter of K8, which regulates glucose metabolism.