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Proteinuria Triggers Renal Lymphangiogenesis Prior to the Development of Interstitial Fibrosis
Proteinuria is an important cause of progressive tubulo-interstitial damage. Whether proteinuria could trigger a renal lymphangiogenic response has not been established. Moreover, the temporal relationship between development of fibrosis, inflammation and lymphangiogenesis in chronic progressive kid...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506584/ https://www.ncbi.nlm.nih.gov/pubmed/23189189 http://dx.doi.org/10.1371/journal.pone.0050209 |
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author | Yazdani, Saleh Poosti, Fariba Kramer, Andrea B. Mirković, Katarina Kwakernaak, Arjan J. Hovingh, Menno Slagman, Maartje C. J. Sjollema, Klaas A. de Borst, Martin H. Navis, Gerjan van Goor, Harry van den Born, Jacob |
author_facet | Yazdani, Saleh Poosti, Fariba Kramer, Andrea B. Mirković, Katarina Kwakernaak, Arjan J. Hovingh, Menno Slagman, Maartje C. J. Sjollema, Klaas A. de Borst, Martin H. Navis, Gerjan van Goor, Harry van den Born, Jacob |
author_sort | Yazdani, Saleh |
collection | PubMed |
description | Proteinuria is an important cause of progressive tubulo-interstitial damage. Whether proteinuria could trigger a renal lymphangiogenic response has not been established. Moreover, the temporal relationship between development of fibrosis, inflammation and lymphangiogenesis in chronic progressive kidney disease is not clear yet. Therefore, we evaluated the time course of lymph vessel (LV) formation in relation to proteinuria and interstitial damage in a rat model of chronic unilateral adriamycin nephrosis. Proteinuria and kidneys were evaluated up to 30 weeks after induction of nephrosis. LVs were identified by podoplanin/VEGFR3 double staining. After 6 weeks proteinuria was well-established, without influx of interstitial macrophages and myofibroblasts, collagen deposition, osteopontin expression (tubular activation) or LV formation. At 12 weeks, a ∼3-fold increase in cortical LV density was found (p<0.001), gradually increasing over time. This corresponded with a significant increase in tubular osteopontin expression (p<0.01) and interstitial myofibroblast numbers (p<0.05), whereas collagen deposition and macrophage numbers were not yet increased. VEGF-C was mostly expressed by tubular cells rather than interstitial cells. Cultured tubular cells stimulated with FCS showed a dose-dependent increase in mRNA and protein expression of VEGF-C which was not observed by human albumin stimulation. We conclude that chronic proteinuria provoked lymphangiogenesis in temporal conjunction with tubular osteopontin expression and influx of myofibroblasts, that preceded interstitial fibrosis. |
format | Online Article Text |
id | pubmed-3506584 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35065842012-11-27 Proteinuria Triggers Renal Lymphangiogenesis Prior to the Development of Interstitial Fibrosis Yazdani, Saleh Poosti, Fariba Kramer, Andrea B. Mirković, Katarina Kwakernaak, Arjan J. Hovingh, Menno Slagman, Maartje C. J. Sjollema, Klaas A. de Borst, Martin H. Navis, Gerjan van Goor, Harry van den Born, Jacob PLoS One Research Article Proteinuria is an important cause of progressive tubulo-interstitial damage. Whether proteinuria could trigger a renal lymphangiogenic response has not been established. Moreover, the temporal relationship between development of fibrosis, inflammation and lymphangiogenesis in chronic progressive kidney disease is not clear yet. Therefore, we evaluated the time course of lymph vessel (LV) formation in relation to proteinuria and interstitial damage in a rat model of chronic unilateral adriamycin nephrosis. Proteinuria and kidneys were evaluated up to 30 weeks after induction of nephrosis. LVs were identified by podoplanin/VEGFR3 double staining. After 6 weeks proteinuria was well-established, without influx of interstitial macrophages and myofibroblasts, collagen deposition, osteopontin expression (tubular activation) or LV formation. At 12 weeks, a ∼3-fold increase in cortical LV density was found (p<0.001), gradually increasing over time. This corresponded with a significant increase in tubular osteopontin expression (p<0.01) and interstitial myofibroblast numbers (p<0.05), whereas collagen deposition and macrophage numbers were not yet increased. VEGF-C was mostly expressed by tubular cells rather than interstitial cells. Cultured tubular cells stimulated with FCS showed a dose-dependent increase in mRNA and protein expression of VEGF-C which was not observed by human albumin stimulation. We conclude that chronic proteinuria provoked lymphangiogenesis in temporal conjunction with tubular osteopontin expression and influx of myofibroblasts, that preceded interstitial fibrosis. Public Library of Science 2012-11-26 /pmc/articles/PMC3506584/ /pubmed/23189189 http://dx.doi.org/10.1371/journal.pone.0050209 Text en © 2012 Yazdani et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yazdani, Saleh Poosti, Fariba Kramer, Andrea B. Mirković, Katarina Kwakernaak, Arjan J. Hovingh, Menno Slagman, Maartje C. J. Sjollema, Klaas A. de Borst, Martin H. Navis, Gerjan van Goor, Harry van den Born, Jacob Proteinuria Triggers Renal Lymphangiogenesis Prior to the Development of Interstitial Fibrosis |
title | Proteinuria Triggers Renal Lymphangiogenesis Prior to the Development of Interstitial Fibrosis |
title_full | Proteinuria Triggers Renal Lymphangiogenesis Prior to the Development of Interstitial Fibrosis |
title_fullStr | Proteinuria Triggers Renal Lymphangiogenesis Prior to the Development of Interstitial Fibrosis |
title_full_unstemmed | Proteinuria Triggers Renal Lymphangiogenesis Prior to the Development of Interstitial Fibrosis |
title_short | Proteinuria Triggers Renal Lymphangiogenesis Prior to the Development of Interstitial Fibrosis |
title_sort | proteinuria triggers renal lymphangiogenesis prior to the development of interstitial fibrosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506584/ https://www.ncbi.nlm.nih.gov/pubmed/23189189 http://dx.doi.org/10.1371/journal.pone.0050209 |
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