Angiotensin II type 2 receptor mediated angiotensin II and high glucose induced decrease in renal prorenin/renin receptor expression.
Activation of prorenin/renin receptor [(P)RR] mediates non-enzymatic pathway for the physiological function of prorenin/renin. It also plays a role in the pathogenesis of diabetic nephropathy. However, the mechanisms of regulating (P)RR expression are only partially understood. In the present study, we examine the change of (P)RR under hyperglycemic conditions in the kidneys of streptozotocin (STZ)-induced diabetic (DM) rats and cultured rat renal glomerular mesangial cells (MCs). The (P)RR mRNA level was significantly lower in the kidney of (DM) rats than that of untreated control animals, meanwhile the plasma and renal angiotensin II (Ang II) levels and Ang II type 2 receptor (AT(2)R) mRNA level, but not Ang II type 1 receptor (AT(1)R) mRNA level were increased in (DM) rats. In cultured MCs, Ang II reduced the (P)RR expression and this inhibitory effect was blocked by the AT(2)R antagonist, PD123319, but not the AT(1)R antagonist, losartan. The AT(2)R agonist CGP42112A produced a similar effect as Ang II. Exposure to high glucose (30mM) resulted in a decrease in the (P)RR expression. PD123319, but not losartan, reversed high glucose induced (P)RR expression reduction. The present results indicate that activation of AT(2)R, but not AT(1)R, is most likely responsible for the reduced (P)RR expression in response to Ang II and high glucose in glomerular MCs and the renal tissue of STZ-treated rats.
He
Ming
M
Department of Physiology and Pathophysiology, Fudan University, Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai 200032, China.
Zhang
Lin
L
Shao
Ying
Y
Xue
Hong
H
Zhou
Li
L
Wang
Xiao-Fang
XF
Yu
Chen
C
Yao
Tai
T
Lu
Li-Min
LM
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D000093342:Prorenin Receptor
D001786:Blood Glucose; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012083:Renin; D005947:Glucose; D000093342:Prorenin Receptor