Investigating MDM2 Regulation of Endothelial Cell Angiomir Biosynthesis in Response to High Glucose Treatment

MiRNAs are a class of short, non-coding RNAs that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA production contributes to the pathogenesis of hyperglycemia-related complications. Although many studies have examined the effect of hyperglycemia on the expression of miRNAs, the effect of hyperglycemia specifically on the endothelial cell miRNA biogenesis machinery is poorly understood.

The aim of my project is to better characterize the effect of high glucose treatment on the miRNA biogenesis machinery and miRNA expression in endothelial cells. HDMECs were incubated with low (5mM) and high (30mM) glucose concentrations for 6 and 24 hours and subsequent miRNA expression was measured.

My results indicate that exposure to high glucose concentrations enhances MDM2:DROSHA binding and represses DROSHA expression both in vitro and in diabetic mice (db/db) muscles. Treatment with MDM2 inhibitors repealed glucose-induced DROSHA downregulation. This suggests that high glucose concentrations downregulates DROSHA expression through an MDM2-mediated mechanism.