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Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy
Objective. Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated. Methods. Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773418/ https://www.ncbi.nlm.nih.gov/pubmed/24069045 http://dx.doi.org/10.1155/2013/941893 |
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author | Stratakis, Stavros Stylianou, Kostas Petrakis, Ioannis Mavroeidi, Vasiliki Poulidaki, Rafaela Petra, Christina Moisiadis, Demitrios Stratigis, Spyros Vardaki, Eleftheria Nakopoulou, Lydia Daphnis, Eugene |
author_facet | Stratakis, Stavros Stylianou, Kostas Petrakis, Ioannis Mavroeidi, Vasiliki Poulidaki, Rafaela Petra, Christina Moisiadis, Demitrios Stratigis, Spyros Vardaki, Eleftheria Nakopoulou, Lydia Daphnis, Eugene |
author_sort | Stratakis, Stavros |
collection | PubMed |
description | Objective. Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated. Methods. Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in 12 Sprague-Dawley male rats. One week later, six of these rats were commenced on daily treatment with subcutaneous rapamycin 0.5 mgr/kg (PHN-Rapa). The remaining six rats were used as the proteinuric control group (PHN) while six more rats without PHN were given the rapamycin solvent and served as the healthy control group (HC). All rats were sacrificed at the end of the 7th week. Results. Rapamycin significantly reduced proteinuria during the autologous phase of PHN. Histological lesions were markedly improved by rapamycin. Immunofluorescence revealed attenuated deposits of autologous alloantibodies in treated rats. Untreated rats showed decreased glomerular content of both nephrin and podocin whereas rapamycin restored their expression. Conclusions. Rapamycin monotherapy significantly improves proteinuria and histological lesions in experimental membranous nephropathy. This beneficial effect may be mediated by inhibition of the alloimmune response during the autologous phase of PHN and by restoration of the normal expression of the podocyte proteins nephrin and podocin. |
format | Online Article Text |
id | pubmed-3773418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-37734182013-09-25 Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy Stratakis, Stavros Stylianou, Kostas Petrakis, Ioannis Mavroeidi, Vasiliki Poulidaki, Rafaela Petra, Christina Moisiadis, Demitrios Stratigis, Spyros Vardaki, Eleftheria Nakopoulou, Lydia Daphnis, Eugene Clin Dev Immunol Research Article Objective. Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated. Methods. Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in 12 Sprague-Dawley male rats. One week later, six of these rats were commenced on daily treatment with subcutaneous rapamycin 0.5 mgr/kg (PHN-Rapa). The remaining six rats were used as the proteinuric control group (PHN) while six more rats without PHN were given the rapamycin solvent and served as the healthy control group (HC). All rats were sacrificed at the end of the 7th week. Results. Rapamycin significantly reduced proteinuria during the autologous phase of PHN. Histological lesions were markedly improved by rapamycin. Immunofluorescence revealed attenuated deposits of autologous alloantibodies in treated rats. Untreated rats showed decreased glomerular content of both nephrin and podocin whereas rapamycin restored their expression. Conclusions. Rapamycin monotherapy significantly improves proteinuria and histological lesions in experimental membranous nephropathy. This beneficial effect may be mediated by inhibition of the alloimmune response during the autologous phase of PHN and by restoration of the normal expression of the podocyte proteins nephrin and podocin. Hindawi Publishing Corporation 2013 2013-08-31 /pmc/articles/PMC3773418/ /pubmed/24069045 http://dx.doi.org/10.1155/2013/941893 Text en Copyright © 2013 Stavros Stratakis et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Stratakis, Stavros Stylianou, Kostas Petrakis, Ioannis Mavroeidi, Vasiliki Poulidaki, Rafaela Petra, Christina Moisiadis, Demitrios Stratigis, Spyros Vardaki, Eleftheria Nakopoulou, Lydia Daphnis, Eugene Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy |
title | Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy |
title_full | Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy |
title_fullStr | Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy |
title_full_unstemmed | Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy |
title_short | Rapamycin Ameliorates Proteinuria and Restores Nephrin and Podocin Expression in Experimental Membranous Nephropathy |
title_sort | rapamycin ameliorates proteinuria and restores nephrin and podocin expression in experimental membranous nephropathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773418/ https://www.ncbi.nlm.nih.gov/pubmed/24069045 http://dx.doi.org/10.1155/2013/941893 |
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