Gestational diabetes (GD) is a common disorder present in human. It is associated with increased levels of glucose in the blood that can be dangerous for neonatal growth. The genetic component is believed not to be a component of the disease as no significant association has been reported. New lines of evidences suggest an epigenetic component for GD. Moreover, exposure of cells to high glucose (HG) conditions is believed to induce epigenetic changes. In order to study epigenetic changes by HG in vivo we compared gene expression and promoter methylation in endothelial primary cell lines from umbilical cords of GD patients (n=3) and controls (n=3). In order to assess the effect of hyperglycemia in vivo we firstly analyzed gene effects at the level of the transcriptome using chips. We found induction of several genes. Many genes were confirmed by means of qPCR. Quantitative PCR of methylation-sensitive or resistant testriction enzyme digested genomic DNA from GD-HUVEC using primers amplifying CpG rich island shows differential DNA methylation in TGFB2 and IGFBP3. Data obtained at the same time brings new information on DG, i.e. the hypothesis of an epigenetic mechanism regulating TGFB2 and IGFBP3 expression by HG and supports the use of GD-HUVEC cells as a model for the study of the molecular mechanisms involved in the pathogenesis of the disease.
Evidence of an epigenetic regulation mechanism in primary endothelial cells from gestational diabetes umbilical cords
2012-01-01
Abstract
Gestational diabetes (GD) is a common disorder present in human. It is associated with increased levels of glucose in the blood that can be dangerous for neonatal growth. The genetic component is believed not to be a component of the disease as no significant association has been reported. New lines of evidences suggest an epigenetic component for GD. Moreover, exposure of cells to high glucose (HG) conditions is believed to induce epigenetic changes. In order to study epigenetic changes by HG in vivo we compared gene expression and promoter methylation in endothelial primary cell lines from umbilical cords of GD patients (n=3) and controls (n=3). In order to assess the effect of hyperglycemia in vivo we firstly analyzed gene effects at the level of the transcriptome using chips. We found induction of several genes. Many genes were confirmed by means of qPCR. Quantitative PCR of methylation-sensitive or resistant testriction enzyme digested genomic DNA from GD-HUVEC using primers amplifying CpG rich island shows differential DNA methylation in TGFB2 and IGFBP3. Data obtained at the same time brings new information on DG, i.e. the hypothesis of an epigenetic mechanism regulating TGFB2 and IGFBP3 expression by HG and supports the use of GD-HUVEC cells as a model for the study of the molecular mechanisms involved in the pathogenesis of the disease.Pubblicazioni consigliate
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