title: (Pro)renin receptor: another member of the system controlled by angiotensin II?
abstract: The prorenin receptor [(P)RR] is upregulated in the diabetic kidney and has been implicated in the high glucose (HG)-induced overproduction of profibrotic molecules by mesangial cells (MCs), which is mediated by ERK1/2 phosphorylation. The regulation of (P)RR gene transcription and the mechanisms by which HG increases (P)RR gene expression are not fully understood. Because intracellular levels of angiotensin II (AngII) are increased in MCs stimulated with HG, we used this in vitro system to evaluate the possible role of AngII in (P)RR gene expression and function by comparing the effects of AT1 receptor blockers (losartan or candesartan) and (P)RR mRNA silencing (siRNA) in human MCs (HMCs) stimulated with HG. HG induced an increase in (P)RR and fibronectin expression and in ERK1/2 phosphorylation. These effects were completely reversed by (P)RR siRNA and losartan but not by candesartan (an angiotensin receptor blocker that, in contrast to losartan, blocks AT1 receptor internalization). These results suggest that (P)RR gene activity may be controlled by intracellular AngII and that HG-induced ERK1/2 phosphorylation and fibronectin overproduction are primarily induced by (P)RR activation. This relationship between AngII and (P)RR may constitute an additional pathway of MC dysfunction in response to HG stimulation.
authors: Department of Medicine, Renal Division, Federal University of São Paulo, São Paulo, Brazil.
authors: Luciana G
authors: LG
authors: Pereira
authors: Carine P
authors: CP
authors: Arnoni
authors: Edgar
authors: E
authors: Maquigussa
authors: Priscila C
authors: PC
authors: Cristovam
authors: Juliana
authors: J
authors: Dreyfuss
authors: Mirian A
authors: MA
authors: Boim
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013997:Time Factors; D014343:Trypan Blue / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D000093342:Prorenin Receptor
chemical_list: D000804:Angiotensin II; D005353:Fibronectins; D005947:Glucose; D019808:Losartan; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011956:Receptors, Cell Surface; D014343:Trypan Blue; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor