Altered subcellular distribution of cadherin-5 in endothelial cells caused by the serum of pre-eclamptic patients
Altered subcellular distribution of cadherin-5 in endothelial cells caused by the serum of pre-eclamptic patients
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DOI：
10.1093/molehr/6.11.1027
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发表时间：
2000-11-01
影响因子：
4
通讯作者：
Wedlich, D
中科院分区：
文献类型：
--
作者：
Groten, T;Kreienberg, R;Wedlich, D
子痫前期的主要临床特征是水肿和血管渗漏。钙粘蛋白-5介导内皮细胞-血管内皮末端的细胞接触可能作为一种血管功能调节通透性。因此，我们研究了子痫前期是否会改变钙粘蛋白-5的表达和细胞内分布。将合流人脐静脉内皮细胞（HUVEC）与20%的子痫前期（n = 18）、溶血-肝酶升高-低血小板综合征（HELLP） （n = 12）、妊高征（PIH） （n = 18）或正常妊娠（n = 10）患者血清孵育。与子痫前期患者的血清孵卵后，免疫染色分析显示钙粘蛋白-5在高尔基体的水泡和管状结构中积累。子痫前期血清孵育后HUVEC的免疫印迹分析显示，稳定形式的钙粘蛋白-5增加，而降解产物减少。cadherin-5的降解发生在细胞膜上，因此这种减少可能是由于细胞膜中cadherin-5的减少。钙粘蛋白-5在高尔基体囊泡和管状结构中的积累表明，钙粘蛋白-5对质膜的靶向可能被破坏。我们认为，子痫前期患者血清因子引起的细胞内钙粘蛋白-5潴留可能减少细胞膜粘附复合物的数量，从而导致内皮功能障碍。
The main clinical features of pre-eclampsia are oedema and vascular leakage. Cadherin-5 mediates endothelial cell-cell contact in the vascular endothelium end may regulate permeability as a vascular function. Therefore, we addressed the question of whether pre-eclampsia alters cadherin-5 expression and intracellular distribution. Confluent human umbilical vein endothelial cells (HUVEC) were incubated with 20% serum from patients with pre-eclampsia (n = 18), haemolysis-elevated liver enzymes-low platelet syndrome (HELLP) (n = 12), pregnancy-induced hypertension (PIH) (n = 18) or normal pregnancy (n = 10). After incubation with sera from patients with pre-eclampsia, immunostaining analyses showed cadherin-5 accumulation in vesicular and tubular structures of the Golgi apparatus. Immunoblot analyses of HUVEC after pre-eclampsia serum incubation showed an increase of the stable form of cadherin-5 while degradation products decreased. Degradation of cadherin-5 takes place at the cell membrane, so this decrease may be due to a decrease of cadherin-5 in the cell membrane. The accumulation of cadherin-5 in the vesicular and tubular structures of the Golgi apparatus indicates that targeting of cadherin-5 to the plasma membrane could be disrupted. We suggest that intracellular retention of cadherin-5 caused by serum factors in patients with pre-eclampsia may decrease the number of adhesion complexes in the cell membrane, thereby contributing to endothelial dysfunction.