Proteomic Characterization of IC Bladder

IC 膀胱的蛋白质组学表征

• 批准号: 7108521
• 负责人: Pradeep Tyagi
• 金额: $ 29.43万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7108521
• 关键词: animal tissue; antibody; biological signal transduction; biomarker; blood tests; diagnosis design /evaluation; disease /disorder etiology; immunocytochemistry; immunofluorescence technique; immunologic assay /test; interstitial cystitis; isoelectric point; laboratory mouse; laboratory rabbit; laboratory rat; nerve growth factors; nitric oxide; protein quantitation /detection; proteomics; two dimensional gel electrophoresis; urinalysis; urinary tract disorder diagnosis; western blottings

DESCRIPTION (provided by applicant): Interstitial cystitis (IC) is a painful bladder syndrome of unknown etiology, characterized by chronic pelvic pain, urinary frequency and urgency. It affects an estimated 700,000 to one million people in the United States; approximately 90% of the reported sufferers are women. Diagnosis of IC is primarily based on symptoms, as there are no currently available blood or urine tests due to the lack of demonstrated biological markers. The nuclear matrix is the structural scaffolding of the cell nucleus and plays a central role in the regulation of important cellular processes. Specific nuclear matrix proteins (NMPs) have been identified as unique to certain cell types or states. Although the estimated number of different proteins in a cell might outnumber the estimated number of genes in the same cell, proteins are the functional players in cell pathophysiology. Therefore, we propose to use a proteomic approach to identify specific new markers related to chronic cystitis. Several agents, such as Nerve Growth Factor (NGF), nitric oxide (NO) and proinflammatory mediators, have been shown to exert an effect in bladder afferent pathways that could be related to frequent voiding and nociceptive responses in chronic cystitis. Thus, two hypotheses will be tested: 1) Alterations in NMPs are characteristic of the bladder with chronic irritation and can be developed into diagnostic markers and/or treatment targets for painful bladder syndrome such as IC. 2) Functional improvement of chronic cystitis after intervention on NGF, NO, and inflammatory pathways, is associated with changes in NMPs. To address these hypotheses, we propose the following Specific Aims: 1) to perform a comprehensive analysis of the nuclear matrix protein composition of the bladder with chronic irritation in comparison to normal controls to identify specific proteins associated with the disease. 2) to characterize and sequence specific nuclear matrix proteins associated with bladders with chronic irritation and to raise antibodies against these markers and to develop diagnostics tests in this regard. 3) to analyze the effect of several modulators of the bladder afferent pathway, NGF, NO and IPD-1151 T, on specific NMPs associated with the pathogenesis of chronic cystitic bladder. The long-term objectives of this research project are to identify new markers that can be used in sensitive, specific test/screens for IC and may prove of immense value in the accurate diagnosis, and even early prediction, of disease. The results of this research project could also identify new molecular targets of drug therapy for chronic bladder and/or pelvic pain associated with painful bladder syndromes, offering a better outcome for patients with IC.

描述（由申请人提供）：间质性膀胱炎（IC）是一种疼痛的膀胱综合症，其病因是慢性骨盆疼痛，尿频和紧迫性的特征。它影响了美国估计有700,000至100万人；大约90％的报告患者是女性。 IC的诊断主要基于症状，因为由于缺乏证明的生物学标记，目前尚无血液或尿液检查。核基质是细胞核的结构支架，在重要细胞过程的调节中起着核心作用。特定的核基质蛋白（NMP）已被确定为某些细胞类型或状态独有的。尽管细胞中不同蛋白质的估计数量可能会超过同一细胞中估计的基因数量，但蛋白质是细胞病理生理学中的功能参与者。因此，我们建议使用蛋白质组学方法来识别与慢性膀胱炎有关的特定新标记。已经证明，几种药物，例如神经生长因子（NGF），一氧化氮（NO）和促炎性介质会在膀胱传入途径中发挥作用，这些途径可能与慢性膀胱炎的频繁无效和伤害性反应有关。因此，将测试两个假设：1）NMP的改变是膀胱的特征，具有慢性刺激，可以发展为诊断标记和/或治疗靶标的疼痛膀胱综合征，例如IC。 2）干预NGF，NO和炎症途径后慢性膀胱炎的功能改善与NMP的变化有关。为了解决这些假设，我们提出以下具体目的：1）与正常对照相比，对膀胱的核基质蛋白组成进行了全面分析，以识别与疾病相关的特定蛋白质。 2）表征和序列特定的核基质蛋白与具有慢性刺激的膀胱相关的膀胱相关，并在这方面提出针对这些标记物的抗体并开发诊断测试。 3）分析膀胱传入途径的几个调节剂NGF，NO和IPD-1151 T的影响，对与慢性尾膀胱的发病机理相关的特定NMP。该研究项目的长期目标是确定可用于IC的敏感，特定的测试/筛选中的新标记物，并可能在准确的诊断甚至早期预测疾病中具有巨大的价值。该研究项目的结果还可以鉴定出与疼痛膀胱综合征相关的慢性膀胱和/或骨盆疼痛的药物治疗的新分子靶标，为IC患者提供了更好的结果。

项目成果

Gender-based reciprocal expression of transforming growth factor-beta1 and the inducible nitric oxide synthase in a rat model of cyclophosphamide-induced cystitis.

• DOI: 10.1186/1476-9255-6-23
• 发表时间: 2009-08-19
• 期刊: Journal of inflammation (London, England)
• 作者: Tyagi P;Tyagi V;Yoshimura N;Witteemer E;Barclay D;Loughran PA;Zamora R;Vodovotz Y
• 通讯作者: Vodovotz Y