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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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.
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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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