Transcriptional Regulation of Insulin and CXCL10 Gene by Peroxisome Proliferator Activated Receptor γ Coactivator-1α

Background: Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which act as a coactivator of nuclear receptors and several other transcription factors. This study was performed to evaluate the expressional regulation of insulin and inflammatory response genes by PGC-1α. Methods: Transient transfection assays were performed to measure the promoter activity of the insulin and CXCL10 gene. The insulin gene expression levels in INS-1 cells were determined by Northern blot analysis. Differentially expressed genes by PGC-1α overexpression in HASMCs were confirmed using DNA microarray, real-time PCR and Northen blot analysis. Results: Insulin promoter activity and mRNA levels were suppressed by GR and Ad-PGC-1α. Northern blot analysis of the INS-1 cells revealed that infection with Ad-PGC-1α markedly reduced the amount of insulin mRNA and treatment of Dex enhanced this effect in an additive manner. The PGC-1α-specific siRNA decreased insulin expression that was induced by Dex in the GR-expressing INS-1 cells was nearly restored by this siRNA treatment. We found that when vascular smooth muscle cells (VSMCs) overexpressed PGC-1α, immune or inflammatory response genes were highly expressed. For example, promoter activity and mRNA level of CXCL10 gene were increased by PGC-1α. Conclusion: PGC-1α overexpression inhibited insulin promoter activity in INS-1 cells and enhanced expressions of inflammatory response genes (CXCL10, CXCL11, TNFLSF10) in VSMCs.