Decreased expression of VE-cadherin and claudin-5 and increased phosphorylation of VE-cadherin in vascular endothelium in nasal polyps.
Decreased expression of VE-cadherin and claudin-5 and increased phosphorylation of VE-cadherin in vascular endothelium in nasal polyps.
复制标题
鼻息肉血管内皮中 VE-cadherin 和 Claudin-5 表达降低，VE-cadherin 磷酸化增加。
DOI：
10.1007/s00441-013-1583-0
复制
发表时间：
2013
期刊：
影响因子：
3.6
通讯作者：
Terada N.
中科院分区：
文献类型：
--
作者：
Yukitatsu Y;Hata M;Yamanegi K;Yamada N;Ohyama H;Nakasho K;Kojima Y;Oka H;Tsuzuki K;Sakagami M;Terada N.
VE-钙粘蛋白和claudin-5是血管内皮细胞粘附和紧密连接的主要成分，其表达的减少和VE-钙粘蛋白酪氨酸磷酸化的增加与内皮细胞旁通透性的增加相关。为了阐明鼻息肉水肿发生的机制，我们研究了息肉微血管中的这些分子。采用免疫荧光双标法对正常下鼻甲粘膜组织和接受或未接受糖皮质激素治疗的鼻息肉进行VE-钙粘蛋白或claudin-5和CD 31染色，免疫荧光强度为1-3级，强度逐渐增加。为了校正可归因于切片中暴露的不同内皮区域或切片厚度的荧光强度差异，通过将每个微血管中VE-钙粘蛋白或密蛋白-5的等级除以CD 31的等级来估计相对免疫荧光强度。通过Western印迹分析检测VE-钙粘蛋白的酪氨酸磷酸化。VE-钙粘蛋白和claudin-5在CD 31阳性微血管中的相对强度按以下顺序显著降低：下鼻甲粘膜、治疗的息肉和未治疗的息肉。酪氨酸磷酸化VE-钙粘蛋白与VE-钙粘蛋白的比率在未治疗的息肉中显著高于下鼻甲粘膜和治疗的息肉，两者之间的比率没有显著差异。因此，在鼻息肉中，内皮粘附和紧密连接的屏障功能减弱，尽管糖皮质激素治疗改善了这种减弱的屏障功能。
VE-cadherin and claudin-5 are major components of adherens and tight junctions of vascular endothelial cells and a decrease in their expression and an increase in the tyrosine-phosphorylation of VE-cadherin are associated with an increase in endothelial paracellular permeability. To clarify the mechanism underlying the development of edema in nasal polyps, we studied these molecules in polyp microvessels. Normal inferior turbinate mucosal tissues and nasal polyps from patients treated with or without glucocorticoid were stained for VE-cadherin or claudin-5 and CD31 by a double-immunofluorescence method and the immunofluorescence intensities were graded 1–3 with increasing intensity. To correct for differences in fluorescence intensity attributable to a different endothelial area being exposed in a section or to the thickness of a section, the relative immunofluorescence intensity was estimated by dividing the grade of VE-cadherin or claudin-5 by that of CD31 in each microvessel. Tyrosine-phosphorylation of VE-cadherin was examined by Western blot analysis. The relative intensities of VE-cadherin and claudin-5 in the CD31-positive microvessels significantly decreased in the following order; inferior turbinate mucosa, treated polyps and untreated polyps. The ratio of tyrosine-phosphorylated VE-cadherin to VE-cadherin was significantly higher in untreated polyps than in the inferior turbinate mucosa and treated polyps, between which no significant difference in the ratio was seen. Thus, in nasal polyps, the barrier function of endothelial adherens and tight junctions is weakened, although glucocorticoid treatment improves this weakened barrier function.