Hauser Paul J, Dozmorov Mikhail G, Bane Barbara L, Slobodov Gennady, Culkin Daniel J, Hurst Robert E
Department of Urology, College of Medicine, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
J Urol. 2008 Feb;179(2):764-9. doi: 10.1016/j.juro.2007.09.022. Epub 2007 Dec 20.
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.
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.
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.
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.
检测蛋白聚糖核心蛋白双糖链蛋白聚糖、核心蛋白聚糖、基底膜聚糖和syndecan-1的表达，以及角蛋白18和20的分化相关标志物，以确定糖胺聚糖层缺失的起源，并更全面地研究间质性膀胱炎中尿路上皮细胞分化的改变。
对27例间质性膀胱炎患者和5例对照的福尔马林固定活检组织进行免疫组织化学标记，以检测上述蛋白，并采用对其他标志物的先前评分方法进行修改后评分。通过苏木精和伊红染色切片对炎症进行评分。结合先前数据和新数据，聚类分析显示了标志物与样本之间的关系。
间质性膀胱炎标本聚为4组，从大多数生物标志物异常到大多数生物标志物正常，但均与正常对照分开聚类。一组间质性膀胱炎标本主要表现为E-钙黏蛋白的异常表达，这可能代表早期异常。生物标志物分为2个主要类别。一类包括硫酸软骨素、基底膜聚糖、双糖链蛋白聚糖、核心蛋白聚糖和紧密连接蛋白ZO-1。另一组包括尿血小板溶素、上皮标志物角蛋白18和20以及该层的形态。E-钙黏蛋白和syndecan-1与其他2个聚类或彼此之间几乎没有关系。炎症与syndecan-1中度相关，但与其他标志物无关。
研究结果强烈提示间质性膀胱炎尿路上皮细胞存在异常分化，屏障功能标志物缺失和分化标志物改变是独立的，且与炎症无关。糖胺聚糖层的缺失与腔面层双糖链蛋白聚糖和基底膜聚糖的缺失有关。
