Heparan sulfate proteoglycan, integrin, and syndecan-4 are mechanosensors mediating cyclic strain-modulated endothelial gene expression in mouse embryonic stem cell-derived endothelial cells Journal Article


Authors: Nikmanesh, M.; Cancel, L. M.; Shi, Z. D.; Tarbell, J. M.
Article Title: Heparan sulfate proteoglycan, integrin, and syndecan-4 are mechanosensors mediating cyclic strain-modulated endothelial gene expression in mouse embryonic stem cell-derived endothelial cells
Abstract: It is widely believed that the differentiation of embryonic stem cells (ESCs) into viable endothelial cells (ECs) for use in vascular tissue engineering can be enhanced by mechanical forces. In our previous work, we reported that shear stress enhanced important EC functional genes on a CD31+/CD45− cell population derived from mouse ESC committed to the EC lineage. In the present study, in contrast to the effects of shear stress on this cell population, we observed that cyclic strain significantly reduced the expression of EC-specific marker genes (vWF, VE-cadherin, and PECAM-1), tight junction protein genes (ZO-1, OCLD, and CLD5), and vasoactive genes (eNOS and ET1), while it did not alter the expression of COX2. Taken together, these studies indicate that only shear stress, not cyclic strain, is a useful mechanical stimulus for enhancing the properties of CD31+/CD45− cells for use as EC in vascular tissue engineering. To begin examining the mechanisms controlling cyclic strain-induced suppression of gene expression in CD31+/CD45− cells, we depleted the heparan sulfate (HS) component of the glycocalyx, blocked integrins, and silenced the HS proteoglycan syndecan-4 in separate experiments. All of these treatments resulted in the reversal of cyclic strain-induced gene suppression. The current study and our previous work provide a deeper understanding of the mechanisms that balance the influence of cyclic strain and shear stress in endothelial cells. © 2019 Wiley Periodicals, Inc.
Keywords: cell proliferation; gene expression; embryonic stem cell; endothelial cells; cell culture; stem cells; embryonic stem cells; tissue engineering; glycoproteins; integrin; sulfur compounds; tissue; integrins; mechanotransduction; endothelial cell; shear stress; shear flow; proteoglycans; glycoclayx; heparan sulfate proteoglycan; cell engineering; cyclic strain; syndecan-4
Journal Title: Biotechnology and Bioengineering
Volume: 116
Issue: 10
ISSN: 0006-3592
Publisher: Wiley Blackwell  
Date Published: 2019-10-01
Start Page: 2730
End Page: 2741
Language: English
DOI: 10.1002/bit.27104
PUBMED: 31282995
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 October 2019 -- Source: Scopus
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  1. Zhongdong Shi
    15 Shi