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Suppression of syndecan-1 expression in endothelial cells by tumor necrosis factor-alpha
V Kainulainen1, L Nelimarkka, H Järveläinen
1Turku Center for Biotechnology and the Department of Medical Biochemistry, University of Turku, 20520 Turku, Finland.
Abstract:
Syndecan-1 is a cell surface proteoglycan that binds extracellular matrix components and modulates the activity of heparin-binding growth factors. The expression of syndecan-1 is modified during development, carcinogenesis, and tissue regeneration. During cutaneous wound healing, syndecan-1 expression is transiently induced in newly-formed capillaries of granulation tissue as well as in proliferating keratinocytes. To study the mechanisms underlying this regulation we investigated the effects of several growth factors/cytokines on syndecan-1 expression in two human cell lines: EA.hy 926 endothelial cells and HaCaT keratinocytes. None of these factors significantly altered syndecan-1 mRNA expression in cultured keratinocytes, but when given to endothelial cells, tumor necrosis factor-alpha (TNF-alpha) specifically and dose-dependently suppressed syndecan-1 expression at both mRNA and protein levels. TNF-alpha reduced the amount of syndecan-1 protein in EA.hy 926 cells in both the presence and absence of serum and, at the same time, induced the expression of intercellular adhesion molecule-1 (ICAM-1). The suppressive effect of TNF-alpha on endothelial syndecan-1 expression was reproducible in in vivo experiments in which TNF-alpha-coated beads were administered directly to healing skin wounds of mice. Data supporting these findings were further obtained by injecting TNF-alpha into an experimental rat granulation tissue model. In this tissue TNF-alpha suppressed syndecan-1 mRNA expression by approximately 80%. These results indicate that TNF-alpha is capable of down-regulating syndecan-1 expression in endothelial cells both in vitro and in vivo and suggest that similar mechanisms may be responsible for the changes in syndecan-1 expression observed during various regenerative, developmental, and malignant processes.
Insights
Tumor necrosis factor-alpha (TNF-alpha) suppresses syndecan-1 expression in endothelial cells. This finding in vitro and in vivo suggests TNF-alpha regulates syndecan-1 during tissue regeneration and development.
Area of Science:
- Cell Biology
- Molecular Biology
- Dermatology
Background:
- Syndecan-1 is a cell surface proteoglycan involved in extracellular matrix binding and growth factor modulation.
- Syndecan-1 expression changes during development, carcinogenesis, and tissue regeneration, notably in wound healing.
- Its role in regulating cellular processes necessitates understanding its expression control.
Purpose of the Study:
- To investigate the effects of growth factors and cytokines on syndecan-1 expression.
- To elucidate the mechanisms regulating syndecan-1 expression in endothelial cells and keratinocytes.
Main Methods:
- Utilized human EA.hy 926 endothelial cells and HaCaT keratinocytes in vitro.
- Administered tumor necrosis factor-alpha (TNF-alpha) to cell cultures and in vivo mouse wound models.
- Quantified syndecan-1 mRNA and protein levels, and intercellular adhesion molecule-1 (ICAM-1) expression.
Main Results:
- TNF-alpha specifically and dose-dependently suppressed syndecan-1 mRNA and protein in endothelial cells, but not keratinocytes.
- In vitro, TNF-alpha reduced syndecan-1 protein and increased ICAM-1 expression in endothelial cells.
- In vivo, TNF-alpha suppressed syndecan-1 mRNA expression in mouse skin wounds and rat granulation tissue by approximately 80%.
Conclusions:
- TNF-alpha down-regulates syndecan-1 expression in endothelial cells both in vitro and in vivo.
- These findings suggest TNF-alpha-mediated regulation of syndecan-1 may be crucial in developmental, regenerative, and malignant processes.