Department of Pathogen Biology and Immunology, Guangzhou Medical University, China.
Acta Biochim Biophys Sin (Shanghai). 2011 Dec;43(12):930-9. doi: 10.1093/abbs/gmr094. Epub 2011 Oct 19.
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.
已经确定，透明质酸（HA）聚糖（nHA）和寡糖（oHA）对血管内皮细胞（EC）的生物学功能产生不同的影响，导致血管生成的调节发生改变。然而，具体的机制尚不清楚。我们的研究集中在 nHA 和 oHA 对 EC 中的 ezrin 和 merlin 蛋白的影响上。通过 siRNA 沉默 ezrin 和 merlin 的表达，研究了 oHA 和 nHA 对 EC 生长以及 ezrin 和 merlin 的 mRNA 表达和激活（磷酸化）的调节作用。结果表明，用 nHA 处理时，ezrin 的表达或激活没有明显变化。用 oHA 处理后，ezrin 的表达和激活明显增加，而 merlin 的表达（包括其磷酸化）没有明显变化。沉默 ezrin 表达后，nHA 刺激的人脐静脉内皮细胞中 merlin 的表达及其磷酸化水平明显升高，而 oHA 则没有明显变化。沉默 merlin 表达后，nHA 诱导的 ezrin 的表达（包括其磷酸化）没有明显变化。相反，用 oHA 处理后，ezrin 的表达及其激活明显改善。结果表明，oHA 促进 EC 增殖的机制可能与 ezrin 的表达和激活有关，而 nHA 抑制 EC 增殖的机制可能与 merlin 的表达和激活有关。
