High glucose up-regulates angiotensin II subtype 2 receptors via interferon regulatory factor-1 in proximal tubule epithelial cells.

Earlier studies have reported an increase in the proximal tubule AT(2) receptor (AT(2)R) expression in diabetes, with a beneficial role in kidney function and blood pressure regulation. Here, we demonstrate that the increase in AT(2)R protein expression is associated with an increased expression of transcription factor IRF-1 in hyperglycemic rat and in high glucose-treated HK2 cells. Knock-down of IRF-1 by siRNA in HK2 cells prevented high glucose-induced AT(2)R up-regulation. The data suggest that IRF-1 is a transcriptional regulator of AT(2)R expression in hyperglycemia, and warrant further studies to understand the physiological role of IRF-1 along with AT(2)R in diabetic kidney.