It seems that this master regulator triggers either some hyperglycaemia-induced effects on the endothelial function, or the expression of certain microRNAs (in particular miR-126, -21 and miR-146a-5p) involved in favouring atherosclerosis.
Knockdown of HIF-1α significantly inhibited SP1 and ROBO4, whereas SP1 down-regulation abolished ROBO4 expression in RPE cells under hyperglycaemia/hypoxia. miR-125b-5p and miR-146a-5p were down-regulated by hyperglycaemia and/or hypoxia.
<b>Objective:</b> It was demonstrated that inflammation and oxidative stress induced by hyperglycemia were closely associated with alteration of miR-146a.
Collectively, our data indicate that treatment of diabetic mice with miR-146a mimics robustly reduces DPN and that suppression of hyperglycemia-induced proinflammatory genes by miR-146a mimics may underlie its therapeutic effect.
Here, we show that miR-146a expression levels decrease in the glomeruli of patients with type 2 diabetes (T2D), which correlates with increased albuminuria and glomerular damage. miR-146a levels are also significantly reduced in the glomeruli of albuminuric BTBR ob/ob mice, indicating its significant role in maintaining podocyte health. miR-146a-deficient mice (miR-146a<sup>-/-</sup>) showed accelerated development of glomerulopathy and albuminuria upon streptozotocin (STZ)-induced hyperglycemia.