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Studying the role of fascin-1 in mechanically stressed podocytes
Glomerular hypertension causes glomerulosclerosis via the loss of podocytes, which are challenged by increased mechanical load. We have demonstrated that podocytes are mechanosensitive. However, the response of podocytes to mechanical stretching remains incompletely understood. Here we demonstrate t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577297/ https://www.ncbi.nlm.nih.gov/pubmed/28855604 http://dx.doi.org/10.1038/s41598-017-10116-4 |
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author | Kliewe, Felix Scharf, Christian Rogge, Henrik Darm, Katrin Lindenmeyer, Maja T. Amann, Kerstin Cohen, Clemens D. Endlich, Karlhans Endlich, Nicole |
author_facet | Kliewe, Felix Scharf, Christian Rogge, Henrik Darm, Katrin Lindenmeyer, Maja T. Amann, Kerstin Cohen, Clemens D. Endlich, Karlhans Endlich, Nicole |
author_sort | Kliewe, Felix |
collection | PubMed |
description | Glomerular hypertension causes glomerulosclerosis via the loss of podocytes, which are challenged by increased mechanical load. We have demonstrated that podocytes are mechanosensitive. However, the response of podocytes to mechanical stretching remains incompletely understood. Here we demonstrate that the actin-bundling protein fascin-1 plays an important role in podocytes that are exposed to mechanical stress. Immunofluorescence staining revealed colocalization of fascin-1 and nephrin in mouse kidney sections. In cultured mouse podocytes fascin-1 was localized along actin fibers and filopodia in stretched and unstretched podocytes. The mRNA and protein levels of fascin-1 were not affected by mechanical stress. By Western blot and 2D-gelelectrophoresis we observed that phospho-fascin-1 was significantly downregulated after mechanical stretching. It is known that phosphorylation at serine 39 (S39) regulates the bundling activity of fascin-1, e.g. required for filopodia formation. Podocytes expressing wild type GFP-fascin-1 and non-phosphorylatable GFP-fascin-1-S39A showed marked filopodia formation, being absent in podocytes expressing phosphomimetic GFP-fascin-1-S39D. Finally, the immunofluorescence signal of phosphorylated fascin-1 was strongly reduced in glomeruli of patients with diabetic nephropathy compared to healthy controls. In summary, mechanical stress dephosphorylates fascin-1 in podocytes in vitro and in vivo thereby fascin-1 may play an important role in the adaptation of podocytes to mechanical forces. |
format | Online Article Text |
id | pubmed-5577297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55772972017-09-06 Studying the role of fascin-1 in mechanically stressed podocytes Kliewe, Felix Scharf, Christian Rogge, Henrik Darm, Katrin Lindenmeyer, Maja T. Amann, Kerstin Cohen, Clemens D. Endlich, Karlhans Endlich, Nicole Sci Rep Article Glomerular hypertension causes glomerulosclerosis via the loss of podocytes, which are challenged by increased mechanical load. We have demonstrated that podocytes are mechanosensitive. However, the response of podocytes to mechanical stretching remains incompletely understood. Here we demonstrate that the actin-bundling protein fascin-1 plays an important role in podocytes that are exposed to mechanical stress. Immunofluorescence staining revealed colocalization of fascin-1 and nephrin in mouse kidney sections. In cultured mouse podocytes fascin-1 was localized along actin fibers and filopodia in stretched and unstretched podocytes. The mRNA and protein levels of fascin-1 were not affected by mechanical stress. By Western blot and 2D-gelelectrophoresis we observed that phospho-fascin-1 was significantly downregulated after mechanical stretching. It is known that phosphorylation at serine 39 (S39) regulates the bundling activity of fascin-1, e.g. required for filopodia formation. Podocytes expressing wild type GFP-fascin-1 and non-phosphorylatable GFP-fascin-1-S39A showed marked filopodia formation, being absent in podocytes expressing phosphomimetic GFP-fascin-1-S39D. Finally, the immunofluorescence signal of phosphorylated fascin-1 was strongly reduced in glomeruli of patients with diabetic nephropathy compared to healthy controls. In summary, mechanical stress dephosphorylates fascin-1 in podocytes in vitro and in vivo thereby fascin-1 may play an important role in the adaptation of podocytes to mechanical forces. Nature Publishing Group UK 2017-08-30 /pmc/articles/PMC5577297/ /pubmed/28855604 http://dx.doi.org/10.1038/s41598-017-10116-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kliewe, Felix Scharf, Christian Rogge, Henrik Darm, Katrin Lindenmeyer, Maja T. Amann, Kerstin Cohen, Clemens D. Endlich, Karlhans Endlich, Nicole Studying the role of fascin-1 in mechanically stressed podocytes |
title | Studying the role of fascin-1 in mechanically stressed podocytes |
title_full | Studying the role of fascin-1 in mechanically stressed podocytes |
title_fullStr | Studying the role of fascin-1 in mechanically stressed podocytes |
title_full_unstemmed | Studying the role of fascin-1 in mechanically stressed podocytes |
title_short | Studying the role of fascin-1 in mechanically stressed podocytes |
title_sort | studying the role of fascin-1 in mechanically stressed podocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577297/ https://www.ncbi.nlm.nih.gov/pubmed/28855604 http://dx.doi.org/10.1038/s41598-017-10116-4 |
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