Altered expression, localization, and phosphorylation of epithelial junctional proteins in celiac disease
Altered expression, localization, and phosphorylation of epithelial junctional proteins in celiac disease
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DOI：
10.1309/dtyra91g8r0ktm8m
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发表时间：
2006-04-01
影响因子：
3.5
通讯作者：
Corazza, GR
中科院分区：
文献类型：
--
作者：
Ciccocioppo, R;Finamore, A;Corazza, GR
我们的目的是研究乳糜泻肠上皮细胞连接的分子组分的表达和定位以及酪氨酸磷酸化水平，这是一种已知影响其细胞分布和功能的现象，并探讨促炎细胞因子的影响。采用抗闭合蛋白、抗闭合小带（ZO）-1、抗E-钙粘蛋白、抗β-连环蛋白和抗磷酸酪氨酸抗体对乳糜泻患者和对照组的十二指肠活检标本进行免疫沉淀、免疫印迹和免疫定位。对在不存在或存在干扰素γ和肿瘤坏死因子α的情况下孵育的过滤生长的Caco-2细胞进行相同的程序。在活动性乳糜泻中，磷酸化ZO-1的缺失和β-连环蛋白的广泛磷酸化可能分别导致闭合蛋白和E-钙粘蛋白的膜定位缺失。在体外系统中显示的影响，这些复合物的组装，证明相反的腹腔样本，因为紧密连接的关注，因为存在的磷酸化ZO-1使occludin定位在膜上的细胞因子。
We aimed to study the expression and localization of the molecular components of enterocyte junctions in celiac disease together with the level of tyrosine phosphorylation, a phenomenon known to affect their cellular distribution and function, and to explore the influence of proinflammatory cytokines. Duodenal biopsy specimens from patients with celiac disease and control subjects were used for immunoprecipitation, immunoblotting, and immunolocalization by using antioccludin, anti-zonula occludens (ZO)-1, anti-E-cadherin, anti-beta-catenin, and antiphosphotyrosine antibodies. The same procedures were carried out on filter-grown Caco-2 cells incubated in the absence or presence of interferon gamma and tumor necrosis factor alpha. In active celiac disease, the absence of a phosphorylated ZO-1 and the extensive phosphorylation of beta-catenin might be responsible for the absence of membranous localization of occludin and E-cadherin, respectively. The in vitro system showed an influence of the cytokines on the assembly of these complexes that proved the opposite to celiac samples as far as tight junctions were concerned because the presence of a phosphorylated ZO-1 enables occludin to localize in the membrane.