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(Pro)renin receptor: another member of the system controlled by angiotensin II?
MedLine Citation:
PMID:  21997900     Owner:  NLM     Status:  Publisher    
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.
Luciana G Pereira; Carine P Arnoni; Edgar Maquigussa; Priscila C Cristovam; Juliana Dreyfuss; Mirian A Boim
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-13
Journal Detail:
Title:  Journal of the renin-angiotensin-aldosterone system : JRAAS     Volume:  -     ISSN:  1752-8976     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100971636     Medline TA:  J Renin Angiotensin Aldosterone Syst     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Medicine, Renal Division, Federal University of São Paulo, São Paulo, Brazil.
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