Universität zu Köln

Jungmann, Oliver, Nikolovska, Katerina, Stock, Christian, Schulz, Jan-Niklas ORCID: 0000-0001-9286-206X, Eckes, Beate, Riethmueller, Christoph, Owens, Rick T., Iozzo, Renato V. and Seidler, Daniela G. (2012). ` The Dermatan Sulfate Proteoglycan Decorin Modulates alpha 2 beta 1 Integrin and the Vimentin Intermediate Filament System during Collagen Synthesis. PLoS One, 7 (12). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

Full text not available from this repository.

Abstract

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 alpha 2 beta 1 integrin at day 6 in Dcn(-/-) fibroblasts, whereas the protein core had no effect on beta 1. 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 beta 1 integrin compared to Dcn(-/-). Furthermore, the alpha 2 beta 1 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 alpha 2 beta 1 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jungmann, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Nikolovska, Katerina UNSPECIFIED UNSPECIFIED UNSPECIFIED Stock, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulz, Jan-Niklas UNSPECIFIED orcid.org/0000-0001-9286-206X UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Riethmueller, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Owens, Rick T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Iozzo, Renato V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Seidler, Daniela G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-476975
DOI:	10.1371/journal.pone.0050809
Journal or Publication Title:	PLoS One
Volume:	7
Number:	12
Date:	2012
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LEUCINE-RICH PROTEOGLYCANS; EHLERS-DANLOS-SYNDROME; GROWTH-FACTOR RECEPTOR; MICE LACKING VIMENTIN; CELL-ADHESION; PROTEIN-VIMENTIN; FACTOR-BETA; MIGRATION; FIBROBLASTS; ACTIVATION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47697