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The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis
BACKGROUND: Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1). The effects of the apelin/APJ system on renal fibrosis still remain unclear. METHODS: We examined the effects of the apelin/APJ system on rena...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
S. Karger AG
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350347/ https://www.ncbi.nlm.nih.gov/pubmed/22619666 http://dx.doi.org/10.1159/000337091 |
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author | Nishida, Masashi Okumura, Yasuko Oka, Tatsujiro Toiyama, Kentaro Ozawa, Seiichiro Itoi, Toshiyuki Hamaoka, Kenji |
author_facet | Nishida, Masashi Okumura, Yasuko Oka, Tatsujiro Toiyama, Kentaro Ozawa, Seiichiro Itoi, Toshiyuki Hamaoka, Kenji |
author_sort | Nishida, Masashi |
collection | PubMed |
description | BACKGROUND: Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1). The effects of the apelin/APJ system on renal fibrosis still remain unclear. METHODS: We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO) model. RESULTS: We obtained the following results: (1) At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS) in the UUO kidney were increased compared to those in the nonobstructed kidney. (2) AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3) Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4) Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group. CONCLUSION: These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis. |
format | Online Article Text |
id | pubmed-3350347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | S. Karger AG |
record_format | MEDLINE/PubMed |
spelling | pubmed-33503472012-05-22 The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis Nishida, Masashi Okumura, Yasuko Oka, Tatsujiro Toiyama, Kentaro Ozawa, Seiichiro Itoi, Toshiyuki Hamaoka, Kenji Nephron Extra Original Paper BACKGROUND: Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1). The effects of the apelin/APJ system on renal fibrosis still remain unclear. METHODS: We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO) model. RESULTS: We obtained the following results: (1) At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS) in the UUO kidney were increased compared to those in the nonobstructed kidney. (2) AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3) Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4) Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group. CONCLUSION: These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis. S. Karger AG 2012-03-07 /pmc/articles/PMC3350347/ /pubmed/22619666 http://dx.doi.org/10.1159/000337091 Text en Copyright © 2012 by S. Karger AG, Basel http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No-Derivative-Works License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Users may download, print and share this work on the Internet for noncommercial purposes only, provided the original work is properly cited, and a link to the original work on http://www.karger.com and the terms of this license are included in any shared versions. |
spellingShingle | Original Paper Nishida, Masashi Okumura, Yasuko Oka, Tatsujiro Toiyama, Kentaro Ozawa, Seiichiro Itoi, Toshiyuki Hamaoka, Kenji The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis |
title | The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis |
title_full | The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis |
title_fullStr | The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis |
title_full_unstemmed | The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis |
title_short | The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis |
title_sort | role of apelin on the alleviative effect of angiotensin receptor blocker in unilateral ureteral obstruction-induced renal fibrosis |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350347/ https://www.ncbi.nlm.nih.gov/pubmed/22619666 http://dx.doi.org/10.1159/000337091 |
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