Urothelial Differentiation in Interstitial Cystitis

描述（由申请人提供）：间质性膀胱炎是一种鲜为人知的综合征，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间质性膀胱炎猫模型中，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，我们建议通过以下具体目的对间质性膀胱炎的尿路上皮分化进行首次系统评估：目的1：评估取自组织的尿路上皮细胞中生物标志物的表达。正常的尿路上皮细胞将从尿路上皮组织（膀胱或输尿管）中采集，并通过流式细胞术、免疫染色、RT-PCR和Northern和Western blotting来评估一组生物标志物的表达。这些研究将证实生物标志物组在确定尿路上皮原位分化的特定阶段中的效用。目的2：研究尿液样本中生物标志物的表达。将收集间质性膀胱炎患者和正常志愿者的尿液样本。将进行尿路上皮分化生物标志物含量的评估。尿液中生物标志物的可溶性形式将通过定性和定量免疫分析进行评估。从尿液样本中回收的细胞也将通过免疫染色、免疫测定和RT-PCR进行检测。生物标志物检测结果将与患者特征进行比较。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式提供信息。

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.