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Heparan sulfate proteoglycan mediates shear stress‐induced endothelial gene expression in mouse embryonic stem cell‐derived endothelial cells
Author(s) -
Nikmanesh Maria,
Shi ZhongDong,
Tarbell John M.
Publication year - 2012
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.23302
Subject(s) - shear stress , mechanotransduction , microbiology and biotechnology , chemistry , gene expression , heparan sulfate , gene knockdown , embryonic stem cell , cell , gene , biology , biochemistry , materials science , composite material
It has been shown that shear stress plays a critical role in promoting endothelial cell (EC) differentiation from embryonic stem cell (ESC)‐derived ECs. However, the underlying mechanisms mediating shear stress effects 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 EC were subjected to shear stress (5 dyn/cm 2 ) for 8 h 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 EC‐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 did not 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. Biotechnol. Bioeng. 2012; 109:583–594. © 2011 Wiley Periodicals, Inc.