Bach1 modulates AKT3 transcription to participate in hyperglycaemia-mediated EndMT in vascular endothelial cells.

Abstract

Hyperglycaemia-mediated endothelial-to-mesenchymal transition (EndMT) is involved in the occurrence and progression of cardiovascular complications in diabetic patients. Previous studies reported that AKT serine/threonine kinase 3 (AKT3) and Bric-a-brac/Tramtrack/Broad (BTB) and cap'n'collar (CNC) homology 1 (bach1) participates in endothelial injury and epithelial-to-mesenchymal transition. In the present study, we proposed that bach1 regulates AKT3 transcription, thus involved in hyperglycaemia-mediated EndMT in vascular endothelium. Our results indicated that hyperglycaemia/high glucose increased AKT3 expression and induced EndMT in aorta of diabetic rats and hyperglycaemic human umbilical vein endothelial cells (HUVECs). Moreover, inhibition of AKT3 expression reversed high glucose-mediated EndMT in HUVECs. Further, hyperglycaemia/high glucose augmented bach1 expression in aorta of diabetic rats and hyperglycaemic HUVECs. Furthermore, si-bach1 countered high glucose-induced AKT3 expression and EndMT in HUVECs. In addition, the effect of bach1 overexpression is similar to that of high glucose treatment, which was reversed by si-AKT3. ChIP assays found bach1 enriched in the promoter region of AKT3. Bach1 overexpression augmented AKT3 promoter activity, which lost after specific binding site mutation. Bach1 was involved in hyperglycaemia-induced EndMT via modulation of AKT3 transcription.