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.
Ali
Quaisar
Q
Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX 77204-5037, USA.
Sabuhi
Rifat
R
Hussain
Tahir
T
D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000494:pharmacology*; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*
D050856:Interferon Regulatory Factor-1; C494259:Irf1 protein, rat; D034741:RNA, Small Interfering; D044139:Receptor, Angiotensin, Type 2; D005947:Glucose