KLF9Modulates The Expression Of Anti-ROS Genes Through Regulating PGC-1α In Mouse Primary Hepatocytes

The imbalance of ROS production and degradation will lead to oxdative stress injury of tissues and cells.Now,oxdative stress is generally considered plays an important role in the development of neurodegenerative and cardiovascular diseases. However, the molecular mechanisms are not well understood. KLF9is highly expressed in the brain and liver; however, the function of KLF9in the regulation of ROS remains unexplored. Peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) is capable of coactivating a number of nuclear receptors and other transcriptional factors involved in the regulation of ROS. To investigate the mechanism of KLF9in the regulation of anti-ROS genes expression. The mouse primary hepatocytes were isolated from the wild-type and KLF9knockout mouse and subsequently H2O2treatment was conducted. We aslo performed KLF9overexpression and knock-down by using Ad-virus system (Ad-KLF9, Ad-shKLF9) in mouse primary hepatocytes isolated from wild-type mouse. and we used PGC-1α rescuing methods in wildtype and KLF9knockout mouse hepatocytes.Quantitative real-time PCR (qRT-PCR) and western blot analysis was further performed to determine the expression of anti-ROS genes including CAT, SOD2and GPx1.The expression of anti-ROS genes was upregualted in wild-type mouse primary hepatocytes following H2O2treatment and the induction of H2O2was dampened in KLF9knockout mouse primary hepatocytes. The dual luciferase reporter assay testified KLF9can activate the promoter of PGC-1α gene.We also demonstrated that enforced expression of KLF9led to an increase of anti-ROS genes expression and KLF9inhibition resulted in a decrease of these genes levels in wild-type mouse primary hepatocytes.And we can know the regulation of KLF9was realized by PGC-1α through rescuing methods. Our data indicate that KLF9represents its impact on the expression of anti-ROS genes through PGC-1α. This study provides a new idea and novel method for the ROS-related diseases.