Heparan sulfate proteoglycan mediates shear stress-induced endothelial gene expression in mouse embryonic stem cell-derived endothelial cells Journal Article
| Authors: | Nikmanesh, M.; Shi, Z. D.; Tarbell, J. M. |
| Article Title: | Heparan sulfate proteoglycan mediates shear stress-induced endothelial gene expression in mouse embryonic stem cell-derived endothelial cells |
| Abstract: | 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 (5dyn/cm2) for 8h 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. © 2011 Wiley Periodicals, Inc. |
| Keywords: | immunohistochemistry; controlled study; unclassified drug; nonhuman; protein localization; animal cell; mouse; phenotype; cell division; gene expression; embryonic stem cell; vasculotropin receptor 2; endothelium cell; endothelial cells; tight junction; cyclooxygenase 2; nucleotide sequence; cell membranes; stem cells; embryonic stem cells; hyaluronic acid; glycoproteins; sulfur compounds; vasculotropin receptor 1; cd31 antigen; cell surface; cell surfaces; mechanotransduction; endothelial nitric oxide synthase; vascular endothelial cadherin; ve-cadherin; endothelin 1; protein zo1; stress-induced; tight junctions; endothelial cell; shear stress; shear flow; heparan sulfates; low density lipoprotein; proteoglycans; glycoclayx; heparan sulfate proteoglycan; chondroitin sulfate; embryonic stems; immunostaining; marker genes; protein genes; stress effects; stress modulation; underlying mechanism; cld5 protein; glycosaminoglycan; heparin lyase; ocld protein; proteoheparan sulfate; von willebrand factor |
| Journal Title: | Biotechnology and Bioengineering |
| Volume: | 109 |
| Issue: | 2 |
| ISSN: | 0006-3592 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2012-02-01 |
| Start Page: | 583 |
| End Page: | 594 |
| Language: | English |
| DOI: | 10.1002/bit.23302 |
| PROVIDER: | scopus |
| PMCID: | PMC3228881 |
| PUBMED: | 21837663 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 January 2012" - "CODEN: BIBIA" - "Source: Scopus" |
