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KMID : 0354720070310040326
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Journal of Korean Diabetes Association
2007 Volume.31 No. 4 p.326 ~ p.335
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Original Articles : Transcriptional Regulation of Insulin and CXCL10 Gene by Peroxisome Proliferator Activated Receptor γ Coactivator-1α
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Jang Won-Gu
Kim Jung-Guk
Kim Bo-Wan
Lee In-Kyu
Kim Eun-Jung
Ryu Seong-Yeol
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Abstract
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Background: 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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KEYWORD
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CXCL10, GR, Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), vascular smooth muscle cells, VSMCs
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