The influence of hyaluronic acid on vascular endothelial cell proliferation and the relationship with ezrin/merlin expression

Abstract

It has been established that hyaluronic acid (HA) glycans (nHA) and oligosaccharide (oHA) exert different effects on the biological function of the vascular endothelial cell (EC), resulting in altered regulation of angiogenesis. However, the specific mechanism is still unclear. Our study focused on the effects of nHA and oHA on the ezrin and merlin proteins in EC. The expression of ezrin and merlin was silenced by siRNA, and the regulation on EC growth as well as the mRNA expression and activation ( phosphorylation) of ezrin and merlin stimulated by oHA and nHA was investigated. The results revealed that when treated with nHA, there was no significant change in ezrin expression or activation. After being treated with oHA, the expression and activation of ezrin were definitively increased whereas there were no obvious changes in merlin expression (including its phosphorylation). With ezrin expression silenced, the expression of merlin as well as its phosphorylation levels in nHA-stimulated human umbilical vein endothelial cells were notably elevated, while there was no significant change induced by oHA. With merlin expression silenced, no obvious change was found in the expression of ezrin (including its phosphorylation) induced by nHA. Conversely, the expression of ezrin and its activation was significantly improved after being treated with oHA. The results suggest that the mechanism for the promotion of EC proliferation by oHA is likely related to the expression and activation of ezrin, and the inhibition of EC proliferation by nHA is likely related to the expression and activation of merlin.

No Influence of Exogenous Hyaluronan on the Behavior of Human Cancer Cells or Endothelial Cell Capillary Formation

“…To evaluate the effect of exogenous HA on angiogenesis in vitro , 10 μg/mL LMWHA or HMWHA was added to HUVECs. This dose of HA was chosen based on previous reports (Mo and others ; Wang and others ). Under conditions with no VEGF or FBS, LMWHA promoted capillary formation (Figure ).…”

Harnessing developmental processes for vascular engineering and regeneration

“…HA, a high-molecular-weight polysaccharide, is well-known as an important ECM component; it regulates vascular development by stimulating EC proliferation and cytokine/GF secretion (Takahashi et al, 2005;Mo et al, 2011). HA can be used in hydrogel scaffolds in conjunction with RGD and MMP-sensitive peptides to support vascular morphogenesis and network formation Yee et al, 2011;Kusuma et al, 2013).…”

Comparison of the Effect of Two Hyaluronic Acid Preparations on Fibroblast and Endothelial Cell Functions Related to Angiogenesis

“…HA plays an important role in maintaining the extracellular matrix structure and regulating intercellular activities, such as cell-cell attachment and cell adhesion, by engaging membrane-bound ligands, glycans, and other HA-binding proteins. Moreover, HA occupies a large hydrodynamic volume that greatly influences the hydration and physical properties of tissues [3].…”