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Original Article Transcriptional Regulation of Insulin and CXCL10 Gene by Peroxisome Proliferator Activated Receptor gamma Coactivator-1alpha.
Won Gu Jang, In Kyu Lee, Eun Jung Kim, Seong Yeol Ryu, Bo Wan Kim, Jung Guk Kim
Diabetes & Metabolism Journal 2007;31(4):326-335
Published online: July 1, 2007
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1Department of Internal Medicine, Kyungpook National University School of Medicine.
2Department of Genetic Engineering, Kyungpook National University.
3Department of Infectious Diseases, Keimyung University School of Medicine.

Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), 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-1alpha. 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-1alpha 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-1alpha. Northern blot analysis of the INS-1 cells revealed that infection with Ad-PGC-1alpha markedly reduced the amount of insulin mRNA and treatment of Dex enhanced this effect in an additive manner. The PGC-1alpha-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-1alpha, immune or inflammatory response genes were highly expressed. For example, promoter activity and mRNA level of CXCL10 gene were increased by PGC-1alpha. CONCLUSION: PGC-1alpha overexpression inhibited insulin promoter activity in INS-1 cells and enhanced expressions of inflammatory response genes (CXCL10, CXCL11, TNFLSF10) in VSMCs.

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