Heparan sulfate proteoglycan mediates shear stress-induced endothelial gene expression in mouse embryonic stem cell-derived endothelial cells
| Autor: | Zhong-Dong Shi, John M. Tarbell, Maria Nikmanesh |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cellular differentiation
Bioengineering Biology Mechanotransduction Cellular Applied Microbiology and Biotechnology Article Glycocalyx Mice chemistry.chemical_compound Gene expression Shear stress Animals Mechanotransduction Embryonic Stem Cells Polysaccharide-Lyases Regulation of gene expression Histocytochemistry Endothelial Cells Membrane Proteins Cell Differentiation Heparan sulfate Molecular biology Biomechanical Phenomena carbohydrates (lipids) Endothelial stem cell Gene Expression Regulation chemistry Stress Mechanical Carrier Proteins Heparan Sulfate Proteoglycans Biotechnology |
| Zdroj: | Biotechnology and Bioengineering. 109:583-594 |
| ISSN: | 0006-3592 |
| Popis: | It has been shown that shear stress plays a critical role in promoting endothelial cell (EC) differentiation from embryonic stem cell (ESC)-derived EC. However, the underlying mechanisms mediating shear stress effect in this process have yet to be investigated. It has been reported that the glycocalyx component heparan sulfate proteoglycan (HSPG) mediates shear stress mechanotransduction in mature EC. In this study, we investigated whether cell surface HSPG plays a role in shear stress modulation of EC phenotype. ESC-derived endothelial cells were subjected to shear stress (5 dyn/cm2) for 8 hours with or without heparinase III (Hep III) that digests heparan sulfate. Immunostaining showed that ESC-derived EC surfaces contain abundant HSPG, which could be cleaved by Hep III. We observed that shear stress significantly increased the expression of vascular endothelial cell-specific marker genes (vWF, VE-cadherin, PECAM-1). The effect of shear stress on expression of tight junction protein genes (ZO-1, OCLD, CLD5) was also evaluated. Shear stress increased the expression of ZO-1 and CLD5, while it didn’t alter the expression of OCLD. Shear stress increased expression of vasodilatory genes (eNOS, COX-2), while it decreased the expression of the vasoconstrictive gene ET1. After reduction of HSPG with Hep III, the shear stress-induced expression of vWF, VE-cadherin, ZO-1, eNOS, and COX-2, were abolished, suggesting that shear stress-induced expression of these genes depends on HSPG. These findings indicate for the first time that HSPG is a mechanosensor mediating shear stress-induced EC differentiation from ESC-derived EC cells. |
| Databáze: | OpenAIRE |
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