Dataset Information
Dysregulated post-transcriptional control of COX-2 gene expression in gestational diabetic endothelial cells.
Ontology highlight
ABSTRACT: Background and purpose
Hyperglycaemic memory describes the progression of diabetic complications during subsequent periods of improved glycaemia. We addressed the hypothesis that transient hyperglycaemia causes aberrant COX-2 expression in HUVEC in response to IL-1? through the induction of long-lasting epigenetic changes involving microRNA-16 (miR-16), a post-transcriptional modulator of COX-2 expression.Experimental approach
Studies were performed on HUVEC collected from women with gestational diabetes mellitus (GDM) (dHUVEC) and normal women (nHUVEC).Key results
In dHUVEC treated with IL-1?, the expression of COX-2 mRNA and protein was enhanced and generation of prostanoids increased (the most abundant was the promitogenic PGF2? ). COX-2 mRNA was more stable in dHUVEC and this was associated with miR-16 down-regulation and c-Myc induction (a suppressor of miR expression). dHUVEC showed increased proliferation in response to IL-1?, which was prevented by a COX-2 inhibitor and PGF2? receptor antagonist. Comparable changes in COX-2 mRNA, miR-16 and c-Myc detected in dHUVEC were produced in nHUVEC exposed to transient high glucose and then stimulated with IL-1? under physiological glucose levels; superoxide anion production was enhanced under these experimental conditions.Conclusions and implications
Our results describe a possible mechanism operating in GDM that links the enhanced superoxide anion production and epigenetic changes, associated with hyperglycaemic memory, to endothelial dysfunction through dysregulated post-transcriptional control of COX-2 gene expression in response to inflammatory stimuli. The association of conventional therapy for glycaemic control with agents affecting inflammatory responses and oxidative stress might lead to a more effective prevention of the complications associated with GDM.
SUBMITTER: Di Francesco L
PROVIDER: S-EPMC4562516 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
Publications
Dysregulated post-transcriptional control of COX-2 gene expression in gestational diabetic endothelial cells.
British journal of pharmacology 20150803 18
<h4>Background and purpose</h4>Hyperglycaemic memory describes the progression of diabetic complications during subsequent periods of improved glycaemia. We addressed the hypothesis that transient hyperglycaemia causes aberrant COX-2 expression in HUVEC in response to IL-1β through the induction of long-lasting epigenetic changes involving microRNA-16 (miR-16), a post-transcriptional modulator of COX-2 expression.<h4>Experimental approach</h4>Studies were performed on HUVEC collected from women ...[more]