Urothelial Differentiation in Interstitial Cystitis

描述(申请人提供)：间质性膀胱炎是一种知之甚少的综合征，包括盆腔疼痛、尿频和尿急。越来越多的证据表明，在间质性膀胱炎患者和自发性猫间质性膀胱炎模型中，成熟分化的尿路上皮抗原和屏障功能丧失。我们已经开发了一组独特的生物标志物，用于不同阶段的尿路上皮分化。在这些探索性研究中，我们建议通过以下特定目的首次对间质性膀胱炎的尿路上皮细胞分化进行系统评价：目的1：评价取自组织的尿路上皮细胞中生物标记物的表达。正常的尿路上皮细胞将从尿路上皮组织(膀胱或输尿管)中获取，并通过流式细胞仪、免疫染色、RT-PCR以及Northern和Western blotting对一组生物标志物的表达进行评估。这些研究将证实生物标记物组合在原位确定特定的尿路上皮分化阶段中的作用。目的：研究尿样中生物标记物的表达。尿样将从间质性膀胱炎患者和正常志愿者身上采集。将进行尿路上皮分化生物标记物含量的评估。尿液中生物标志物的可溶形式将通过定性和定量免疫分析进行评估。从尿样中回收的细胞也将通过免疫染色、免疫分析和RT-PCR进行检测。生物标志物分析的结果将与患者的特征进行比较。这些探索性研究将开发一系列新的生物标志物，可能为间质性膀胱炎的诊断、患者分层和有效使用治疗方法提供信息。

DESCRIPTION (provided by applicant): Interstitial cystitis is a poorly understood syndrome that includes pelvic pain, frequent urination and urinary urgency. There is increasing evidence that mature differentiated urothelial antigens and barrier functions are lost in patients with interstitial cystitis and in a spontaneous cat model of interstitial cystitis. We have developed a unique panel of biomarkers for different stages of urothelial differentiation. In these exploratory studies, we propose to perform the first systematic evaluation of urothelial differentiation in interstitial cystitis through the following Specific Aims: Aim 1: to evaluate the expression of biomarkers in urothelial cells taken from tissues. Normal urothelial cells will be harvested from urothelial tissues (bladder or ureter) and evaluated by flow cytometry, immunostaining, RT-PCR and Northern and Western blotting for expression of a panel of biomarkers. These studies will confirm the utility of the biomarker panel in defining specific stages of urothelial differentiation in situ. Aim 2: to study biomarker expression in urine samples. Urine samples will be collected from interstitial cystitis patients and normal volunteers. Evaluation of urothelial differentiation biomarker content will be performed. Soluble forms of the biomarkers in the urine will be evaluated by qualitative and quantitative immunoassay. Cells recovered from the urine sample will also be tested by immunostaining, immunoassay, and RT-PCR. Results of the biomarker assays will be compared to patient characteristics. These exploratory studies will develop a new series of biomarkers that may be informative for the diagnosis, patient stratification and effective use of treatment modalities for interstitial cystitis.