Chondroitin sulfate prevents platelet derived growth factor-mediated phosphorylation of PDGF-Rβ in normal human fibroblasts severely impairing mitogenic responses
✍ Scribed by E. Fthenou; A. Zafiropoulos; P. Katonis; A. Tsatsakis; N.K. Karamanos; G.N. Tzanakakis
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 310 KB
- Volume
- 103
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Platelet‐derived growth factor (PDGF) is a major polypeptide mitogen for cells of mesenchymal origin such as fibroblasts. Chondroitin sulfate chains (CS), which are abundant in the extracellular matrix have been shown to physically interact with PDGF‐BB modulating its biological function. The aim of the present study was to examine the involvement of CS on PDGF‐BB induced proliferative responses and receptor activation in human lung fibroblasts. The addition of exogenous free CS chains caused a significant downregulation of the PDGF‐BB mediated mitogenic and chemotactic responses. Similar results were obtained by the increase of endogenous CS biosynthesis after β‐D‐xyloside treatment. Furthermore, removal of the membrane‐bound CS chains by selective enzymatic treatment significantly increased the proliferative capacity of human fibroblasts. Analysis of PDGF‐R phosphorylation in the presence of CS or β‐D‐xyloside, revealed a reduction of PDGF‐Rβ phosphorylation in the tyrosine residue 1021. These results demonstrate, for the first time, that CS either soluble or surface bound downregulates the mitogenic responses of PDGF‐BB in normal human lung fibroblasts through the reduction of PDGF‐Rβ phosphorylation. J. Cell. Biochem. 103: 1866–1876, 2007. © 2007 Wiley‐Liss, Inc.