The influence of hyaluronic acid on vascular endothelial cell proliferation and the relationship with ezrin/merlin expression
The influence of hyaluronic acid on vascular endothelial cell proliferation and the relationship with ezrin/merlin expression
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透明质酸对血管内皮细胞增殖的影响及与ezrin/merlin表达的关系
DOI：
10.1093/abbs/gmr094
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发表时间：
2011-12-01
影响因子：
3.7
通讯作者：
Gao, Feng
中科院分区：
文献类型：
--
作者：
Mo, Wei;Yang, Cuixia;Gao, Feng
已经确定透明质酸（HA）、聚糖（nHA）和寡糖（oHA）对血管内皮细胞（EC）的生物学功能发挥不同的作用，导致血管生成的调节改变。但具体机制尚不清楚。我们的研究集中在nHA和oHA对EC中ezrin和merlin蛋白的影响。通过siRNA沉默ezrin和merlin的表达，研究oHA和nHA对EC生长以及ezrin和merlin的mRNA表达和激活（磷酸化）的调控。结果显示，当用nHA处理时，ezrin表达或活化没有显著变化。在用oHA处理后，ezrin的表达和活化明确增加，而merlin的表达（包括其磷酸化）没有明显变化。ezrin表达沉默后，nHA刺激的人脐静脉内皮细胞中merlin的表达及其磷酸化水平显著升高，而oHA对merlin的表达及其磷酸化水平无明显影响。在merlin表达沉默的情况下，nHA诱导的ezrin表达（包括其磷酸化）没有明显变化。相反，ezrin的表达及其活化在用oHA处理后显著改善。结果提示，oHA促进EC增殖的机制可能与ezrin的表达和激活有关，nHA抑制EC增殖的机制可能与merlin的表达和激活有关。
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.