(Pro)renin receptor: another member of the system controlled by angiotensin II?
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2012-03-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320311423280 |
| _version_ | 1797283593568911360 |
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| author | Luciana G Pereira Carine P Arnoni Edgar Maquigussa Priscila C Cristovam Juliana Dreyfuss Mirian A Boim |
| author_facet | Luciana G Pereira Carine P Arnoni Edgar Maquigussa Priscila C Cristovam Juliana Dreyfuss Mirian A Boim |
| author_sort | Luciana G Pereira |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T17:34:00Z |
| format | Article |
| id | doaj.art-4c6056215720459b8ca91287275f7c01 |
| institution | Directory Open Access Journal |
| issn | 1470-3203 1752-8976 |
| language | English |
| last_indexed | 2024-03-07T17:34:00Z |
| publishDate | 2012-03-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-4c6056215720459b8ca91287275f7c012024-03-02T17:16:06ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762012-03-011310.1177/1470320311423280(Pro)renin receptor: another member of the system controlled by angiotensin II?Luciana G PereiraCarine P ArnoniEdgar MaquigussaPriscila C CristovamJuliana DreyfussMirian A BoimThe 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.https://doi.org/10.1177/1470320311423280 |
| spellingShingle | Luciana G Pereira Carine P Arnoni Edgar Maquigussa Priscila C Cristovam Juliana Dreyfuss Mirian A Boim (Pro)renin receptor: another member of the system controlled by angiotensin II? Journal of the Renin-Angiotensin-Aldosterone System |
| title | (Pro)renin receptor: another member of the system controlled by angiotensin II? |
| title_full | (Pro)renin receptor: another member of the system controlled by angiotensin II? |
| title_fullStr | (Pro)renin receptor: another member of the system controlled by angiotensin II? |
| title_full_unstemmed | (Pro)renin receptor: another member of the system controlled by angiotensin II? |
| title_short | (Pro)renin receptor: another member of the system controlled by angiotensin II? |
| title_sort | pro renin receptor another member of the system controlled by angiotensin ii |
| url | https://doi.org/10.1177/1470320311423280 |
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