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桥粒芯糖蛋白异常定位与干燥综合征唾液腺腺泡结构紊乱相关。

Aberrant localization of ezrin correlates with salivary acini disorganization in Sjogren's Syndrome.

机构信息

Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Casilla 70061, Santiago 7, Chile.

出版信息

Rheumatology (Oxford). 2010 May;49(5):915-23. doi: 10.1093/rheumatology/keq033. Epub 2010 Feb 25.

Abstract

OBJECTIVES

To analyse whether the alterations in the structure and organization of microvilli in salivary acinar cells from SS patients are linked to changes in the expression and/or cellular localization of ezrin.

METHODS

Salivary gland (SG) acini from controls and SS patients were used to evaluate ezrin expression by western blot and localization of total and activated (phospho-Thr567) ezrin by IF and EM.

RESULTS

In acini from control labial SGs, ezrin was located predominantly at the apical pole and to a lesser extent at the basal region of these cells. Conversely, in acini extracts from SS patients, ezrin showed significantly elevated levels, which were accompanied with localization mostly at the basal region. Moreover, F-actin maintained its distribution in both the apical region and basolateral cortex; however, it was also observed in the acinar cytoplasm. Phospho-ezrin (active form) was located exclusively at the apical pole of acinar cells from control subjects and abundantly located at the basal cytoplasm in SS samples. These results were confirmed by immunogold studies.

CONCLUSIONS

The decrease of ezrin and phospho-ezrin at the apical pole and the cytoplasmic redistribution of F-actin suggest an altered interaction between the F-actin-cytoskeleton and plasma membrane in SS patient acini, which may explain the microvilli disorganization. These alterations could eventually contribute to SG hyposecretion in SS patients.

摘要

目的

分析干燥综合征(SS)患者唾液腺腺泡细胞中微绒毛结构和组织的改变是否与埃兹蛋白(ezrin)的表达和/或细胞定位变化有关。

方法

使用来自对照和 SS 患者的唾液腺(SG)腺泡评估 Western blot 中 ezrin 的表达和 IF 和 EM 中总 ezrin 和激活(磷酸化 Thr567)ezrin 的定位。

结果

在来自对照唇 SG 的腺泡中,ezrin 主要位于细胞的顶端极,在基底区域的表达较少。相反,在 SS 患者的腺泡提取物中,ezrin 显示出显著升高的水平,其定位主要在基底区域。此外,F-肌动蛋白保持在顶端区域和基底侧皮质中的分布;然而,也观察到在腺泡细胞质中。磷酸化 ezrin(活性形式)仅位于对照受试者的腺泡细胞的顶端极,而在 SS 样本中大量位于基底细胞质中。免疫金研究证实了这些结果。

结论

在 SS 患者的腺泡中,ezrin 和磷酸化 ezrin 在顶端极的减少和 F-肌动蛋白的细胞质再分布表明 F-肌动蛋白细胞骨架和质膜之间的相互作用发生改变,这可能解释了微绒毛的紊乱。这些改变最终可能导致 SS 患者的 SG 分泌减少。

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