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The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis
Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(−/−)...
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/PMC3513320/ https://www.ncbi.nlm.nih.gov/pubmed/23226541 http://dx.doi.org/10.1371/journal.pone.0050809 |
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author | Jungmann, Oliver Nikolovska, Katerina Stock, Christian Schulz, Jan-Niklas Eckes, Beate Riethmüller, Christoph Owens, Rick T. Iozzo, Renato V. Seidler, Daniela G. |
author_facet | Jungmann, Oliver Nikolovska, Katerina Stock, Christian Schulz, Jan-Niklas Eckes, Beate Riethmüller, Christoph Owens, Rick T. Iozzo, Renato V. Seidler, Daniela G. |
author_sort | Jungmann, Oliver |
collection | PubMed |
description | Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(−/−)) mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(−/−) mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(−/−) fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, we identified vimentin as one of the proteins that was differentially upregulated by the presence of decorin. We discovered that a decorin-deficient matrix leads to abnormal nuclear morphology in the Dcn(−/−) fibroblasts. This phenotype could be rescued by the decorin proteoglycan but less efficiently by the decorin protein core. Decorin treatment led to a significant reduction of the α2β1 integrin at day 6 in Dcn(−/−) fibroblasts, whereas the protein core had no effect on β1. Interestingly, only the decorin core induced mRNA synthesis, phosphorylation and de novo synthesis of vimentin indicating that the proteoglycan decorin in the extracellular matrix stabilizes the vimentin intermediate filament system. We could support these results in vivo, because the dermis of wild-type mice have more vimentin and less β1 integrin compared to Dcn(−/−). Furthermore, the α2β1 null fibroblasts also showed a reduced amount of vimentin compared to wild-type. These data show for the first time that decorin has an impact on the biology of α2β1 integrin and the vimentin intermediate filament system. Moreover, our findings provide a mechanistic explanation for the reported defects in wound healing associated with the Dcn(−/−) phenotype. |
format | Online Article Text |
id | pubmed-3513320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35133202012-12-05 The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis Jungmann, Oliver Nikolovska, Katerina Stock, Christian Schulz, Jan-Niklas Eckes, Beate Riethmüller, Christoph Owens, Rick T. Iozzo, Renato V. Seidler, Daniela G. PLoS One Research Article Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(−/−)) mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(−/−) mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(−/−) fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, we identified vimentin as one of the proteins that was differentially upregulated by the presence of decorin. We discovered that a decorin-deficient matrix leads to abnormal nuclear morphology in the Dcn(−/−) fibroblasts. This phenotype could be rescued by the decorin proteoglycan but less efficiently by the decorin protein core. Decorin treatment led to a significant reduction of the α2β1 integrin at day 6 in Dcn(−/−) fibroblasts, whereas the protein core had no effect on β1. Interestingly, only the decorin core induced mRNA synthesis, phosphorylation and de novo synthesis of vimentin indicating that the proteoglycan decorin in the extracellular matrix stabilizes the vimentin intermediate filament system. We could support these results in vivo, because the dermis of wild-type mice have more vimentin and less β1 integrin compared to Dcn(−/−). Furthermore, the α2β1 null fibroblasts also showed a reduced amount of vimentin compared to wild-type. These data show for the first time that decorin has an impact on the biology of α2β1 integrin and the vimentin intermediate filament system. Moreover, our findings provide a mechanistic explanation for the reported defects in wound healing associated with the Dcn(−/−) phenotype. Public Library of Science 2012-12-03 /pmc/articles/PMC3513320/ /pubmed/23226541 http://dx.doi.org/10.1371/journal.pone.0050809 Text en © 2012 Jungmann 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 Jungmann, Oliver Nikolovska, Katerina Stock, Christian Schulz, Jan-Niklas Eckes, Beate Riethmüller, Christoph Owens, Rick T. Iozzo, Renato V. Seidler, Daniela G. The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis |
title | The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis |
title_full | The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis |
title_fullStr | The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis |
title_full_unstemmed | The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis |
title_short | The Dermatan Sulfate Proteoglycan Decorin Modulates α2β1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis |
title_sort | dermatan sulfate proteoglycan decorin modulates α2β1 integrin and the vimentin intermediate filament system during collagen synthesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513320/ https://www.ncbi.nlm.nih.gov/pubmed/23226541 http://dx.doi.org/10.1371/journal.pone.0050809 |
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