(Pro)renin receptor: another member of the system controlled by angiotensin II?

(Pro)renin receptor: another member of the system controlled by angiotensin II?

Author Pereira, Luciana Guilhermino Autor UNIFESP Google Scholar
Arnoni, Carine Prisco Autor UNIFESP Google Scholar
Maquigussa, Edgar Autor UNIFESP Google Scholar
Cristovam, Priscila Cardoso Autor UNIFESP Google Scholar
Dreyfuss, Juliana Autor UNIFESP Google Scholar
Boim, Mirian Aparecida Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
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.
Keywords Angiotensin II
glucose
losartan
mesangial cell
(pro)renin receptor
Language English
Date 2012-03-01
Published in Journal of the Renin-angiotensin-aldosterone System. London: Sage Publications Ltd, v. 13, n. 1, p. 1-10, 2012.
ISSN 1470-3203 (Sherpa/Romeo, impact factor)
Publisher Sage Publications Ltd
Extent 1-10
Origin http://dx.doi.org/10.1177/1470320311423280
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000300993400001
URI http://repositorio.unifesp.br/handle/11600/34645

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