title: Angiotensin II type 2 receptor mediated angiotensin II and high glucose induced decrease in renal prorenin/renin receptor expression.
abstract: 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.
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University, Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai 200032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: He
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.forename: Tai
authors.initials: T
authors.lastname: Yao
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Lu
mesh_terms: 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
chemical_list: 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