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ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation
OBJECTIVE: The objective of this article is to test the effects of angiotensin-converting enzyme (ACE)-inhibition on glomerular epithelial cell number in an inducible experimental model of focal segmental glomerulosclerosis (FSGS). BACKGROUND: Although ACE-inhibition has been shown to limit podocyte...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412792/ https://www.ncbi.nlm.nih.gov/pubmed/25143333 http://dx.doi.org/10.1177/1470320314543910 |
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author | Zhang, Jiong Yanez, David Floege, Anna Lichtnekert, Julia Krofft, Ronald D Liu, Zhi-Hong Pippin, Jeffrey W Shankland, Stuart J |
author_facet | Zhang, Jiong Yanez, David Floege, Anna Lichtnekert, Julia Krofft, Ronald D Liu, Zhi-Hong Pippin, Jeffrey W Shankland, Stuart J |
author_sort | Zhang, Jiong |
collection | PubMed |
description | OBJECTIVE: The objective of this article is to test the effects of angiotensin-converting enzyme (ACE)-inhibition on glomerular epithelial cell number in an inducible experimental model of focal segmental glomerulosclerosis (FSGS). BACKGROUND: Although ACE-inhibition has been shown to limit podocyte loss by enhancing survival, little is known about its effect on podocyte number following an abrupt decline in disease. METHODS: Experimental FSGS was induced with cytotoxic antipodocyte antibody. Following induction, groups were randomized to receive the ACE-inhibitor enalapril, the smooth muscle relaxant hydralazine (blood pressure control) or drinking water. Blood pressure, kidney function and histology were measured seven and 14 days following disease induction. RESULTS: Both glomerulosclerosis and urinary albumin-to-creatinine ratio were less in the ACE-inhibition arm at day 14. At day 7 of disease, mean podocyte numbers were 26% and 29% lower in the enalapril and hydralazine arms, respectively, compared to normal mice in which no antibody was injected. At day 14, the mean podocyte number was only 18% lower in the enalapril arm, but was 39% lower in the hydralazine arm compared to normal mice. Podocyte proliferation did not occur at any time in any group. Compared to water- or hydralazine-treated mice with FSGS, the enalapril arm had a higher mean number of glomerular parietal epithelial cells that co-expressed the podocyte proteins WT-1 and synaptopodin, as well as phospho-ERK. CONCLUSION: The results show following an abrupt decline in podocyte number, the initiation of ACE-inhibition but not hydralazine, was accompanied by higher podocyte number in the absence of proliferation. This was accompanied by a higher number of parietal epithelial cells that co-express podocyte proteins. Increasing podocyte number appears to be accompanied by reduced glomerulosclerosis. |
format | Online Article Text |
id | pubmed-4412792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-44127922015-06-15 ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation Zhang, Jiong Yanez, David Floege, Anna Lichtnekert, Julia Krofft, Ronald D Liu, Zhi-Hong Pippin, Jeffrey W Shankland, Stuart J J Renin Angiotensin Aldosterone Syst Article OBJECTIVE: The objective of this article is to test the effects of angiotensin-converting enzyme (ACE)-inhibition on glomerular epithelial cell number in an inducible experimental model of focal segmental glomerulosclerosis (FSGS). BACKGROUND: Although ACE-inhibition has been shown to limit podocyte loss by enhancing survival, little is known about its effect on podocyte number following an abrupt decline in disease. METHODS: Experimental FSGS was induced with cytotoxic antipodocyte antibody. Following induction, groups were randomized to receive the ACE-inhibitor enalapril, the smooth muscle relaxant hydralazine (blood pressure control) or drinking water. Blood pressure, kidney function and histology were measured seven and 14 days following disease induction. RESULTS: Both glomerulosclerosis and urinary albumin-to-creatinine ratio were less in the ACE-inhibition arm at day 14. At day 7 of disease, mean podocyte numbers were 26% and 29% lower in the enalapril and hydralazine arms, respectively, compared to normal mice in which no antibody was injected. At day 14, the mean podocyte number was only 18% lower in the enalapril arm, but was 39% lower in the hydralazine arm compared to normal mice. Podocyte proliferation did not occur at any time in any group. Compared to water- or hydralazine-treated mice with FSGS, the enalapril arm had a higher mean number of glomerular parietal epithelial cells that co-expressed the podocyte proteins WT-1 and synaptopodin, as well as phospho-ERK. CONCLUSION: The results show following an abrupt decline in podocyte number, the initiation of ACE-inhibition but not hydralazine, was accompanied by higher podocyte number in the absence of proliferation. This was accompanied by a higher number of parietal epithelial cells that co-express podocyte proteins. Increasing podocyte number appears to be accompanied by reduced glomerulosclerosis. 2014-08-20 2015-06 /pmc/articles/PMC4412792/ /pubmed/25143333 http://dx.doi.org/10.1177/1470320314543910 Text en http://www.creativecommons.org/licenses/by-nc/3.0/ Creative Commons CC-BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm). Reprints and permissions: sagepub.co.uk/journalsPermissions.nav |
spellingShingle | Article Zhang, Jiong Yanez, David Floege, Anna Lichtnekert, Julia Krofft, Ronald D Liu, Zhi-Hong Pippin, Jeffrey W Shankland, Stuart J ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation |
title | ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation |
title_full | ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation |
title_fullStr | ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation |
title_full_unstemmed | ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation |
title_short | ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation |
title_sort | ace-inhibition increases podocyte number in experimental glomerular disease independent of proliferation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412792/ https://www.ncbi.nlm.nih.gov/pubmed/25143333 http://dx.doi.org/10.1177/1470320314543910 |
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