Abnormal expression of differentiation related proteins and proteoglycan core proteins in the urothelium of patients with interstitial cystitis
Abnormal expression of differentiation related proteins and proteoglycan core proteins in the urothelium of patients with interstitial cystitis
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DOI：
10.1016/j.juro.2007.09.022
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发表时间：
2008-02-01
影响因子：
6.6
通讯作者：
Hurst, Robert E.
中科院分区：
文献类型：
--
作者：
Hauser, Paul J.;Dozmorov, Mikhail G.;Hurst, Robert E.
目的：检测蛋白多糖核心蛋白双糖链蛋白聚糖、核心蛋白聚糖、串珠蛋白聚糖和多配体蛋白聚糖-1的表达，以及角蛋白18和20的分化相关标记，以确定糖胺聚糖层丢失的起源，并更全面地研究间质性膀胱炎中尿路上皮的分化改变。材料和方法：对27例间质性膀胱炎患者和5例对照组的福尔马林固定活检组织进行化学标记，以确定所描述的蛋白质，并使用先前对其他标记物评分的修改进行评分。根据苏木精和伊红染色的载玻片对炎症进行评分。结果：间质性膀胱炎患者分为4组，从大部分生物标志物异常到大部分生物标志物正常，但均与正常对照组不同。一组间质性膀胱炎标本主要表现为E-cadherin的异常表达，这可能是一种早期异常。生物标志物分为2大类。一组由硫酸软骨素、串珠蛋白聚糖、双糖蛋白聚糖、核心蛋白聚糖和紧密连接蛋白ZO-1组成。第二个簇由尿斑蛋白（上皮标记物角蛋白18和20）以及该层的形态组成。E-cadherin和syndecan-1与其他2个簇或彼此之间关系不大。炎症与syndecan-1中度相关，但没有其他marker.Conclusions：研究结果强烈建议异常分化的间质性膀胱炎尿路上皮与屏障功能标志物和改变分化标志物的损失是独立的，独立发生的炎症。糖胺聚糖层的损失与管腔层上双糖链聚糖和串珠蛋白聚糖的损失相关。
Purpose: Expression of the proteoglycan core proteins biglycan, decorin, perlecan and syndecan-1, and differentiation related markers of keratins 18 and 20 were examined to determine the origins of the loss of the glycosaminoglycan layer and investigate more fully the altered differentiation of the urothelium in interstitial cystitis.Materials and Methods: Formalin fixed biopsies from 27 patients with interstitial cystitis and 5 controls were immunohistochemically labeled for the described proteins and scored using a modification of previous scoring for other markers. Inflammation was scored from hematoxylin and eosin stained slides. By combining previous with new data, cluster analysis showed the relationships among the markers and samples.Results: Interstitial cystitis specimens clustered into 4 groups, ranging from most biomarkers abnormal to most biomarkers normal, but all clustered separately from normal controls. One group of interstitial cystitis specimens mainly showed aberrant expression of E-cadherin, which might represent an early abnormality. The biomarkers fell into 2 major groupings. One group consisted of chondroitin sulfate, perlecan, biglycan, decorin and the tight junction protein ZO-1. A second cluster consisted of uroplakin, the epithelial marker keratin 18 and 20, and the morphology of the layer. E-cadherin and syndecan-1 showed little relation to the other 2 clusters or to each other. Inflammation correlated moderately with syndecan-1 but to no other marker.Conclusions: Findings strongly suggest abnormal differentiation in the interstitial cystitis urothelium with a loss of barrier function markers and altered differentiation markers being independent and occurring independently of inflammation. Loss of the glycosaminoglycan layer was associated with a loss of biglycan and perlecan on the luminal layer.