Urine Antiproliferative Peptide in Interstitial Cystitis

间质性膀胱炎中的尿液抗增殖肽

• 批准号: 6845147
• 负责人: Susan F. Keay
• 金额: $ 20.5万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845147
• 关键词: Escherichia coli; adult human (21+); biopsy; cell growth regulation; cell proliferation; disease /disorder model; epidermal growth factor; glycopeptides; heparin; high performance liquid chromatography; human subject; immunocytochemistry; inhibitor /antagonist; interstitial cystitis; laboratory mouse; patient oriented research; peptide structure; pharmacology; protein purification; spectrometry; tissue /cell culture; urinary bladder epithelium

DESCRIPTION (Adapted from the Applicant's Abstract): Interstitial cystitis (IC) is a chronic bladder disease with often devastating effects on the lives of approximately 450,000 people in the U.S. The etiology of IC is unknown, and there is currently no reliably effective treatment. It is therefore important to continue to search for a cause of this debilitating disorder in order to systematically devise an effective therapy. The applicants report discovering two, specific and significant abnormalities in the urine of IC patients as compared to controls, which may be linked to the pathogenesis of this disease - the presence of a low molecular weight urine peptide that inhibits the proliferation of bladder epithelial cells in vitro (antiproliferative factor, or APF) and complex changes in the levels of specific urine epithelial cell growth factors, including significantly decreased urine levels of heparin-binding epidermal growth factor-like growth factor. Because a damaged bladder epithelium is a central finding in IC, it is possible that the APF and the growth factor abnormalities are directly involved in the pathogenesis of this disease. The proposed research is designed to determine the mechanisms by which the APF regulates bladder epithelial cell proliferation. In addition, specific effects of HPLC-purified APF on bladder epithelial cell physiology in vitro will be confirmed in vivo using a mouse model. The applicants suggest data from these studies should yield valuable information regarding the regulation of bladder epithelial proliferation and the pathogenesis of IC.

描述（改编自申请人的摘要）：间质性膀胱炎（IC） 是一种慢性膀胱疾病，经常对 在美国，大约有450,000人IC的病因尚不清楚，并且 目前没有可靠的有效治疗方法。因此很重要 继续寻找这种使人衰弱障碍的原因 系统地设计有效的疗法。 申请人报告发现两个特定和明显的异常 与对照组相比，在IC患者的尿液中，可能与 这种疾病的发病机理 - 存在低分子量尿液的存在 在体外抑制膀胱上皮细胞增殖的肽 （抗增生因子或APF）以及复杂的变化 特定的尿液上皮细胞生长因子，包括显着 肝素结合表皮生长因子样生长的尿液水平降低 因素。因为受损的膀胱上皮是IC中的一个中心发现，所以 APF和生长因子异常可能直接涉及 在这种疾病的发病机理中。 拟议的研究旨在确定APF的机制 调节膀胱上皮细胞增殖。另外，特定效果 膀胱上皮细胞生理学上的HPLC纯化APF的体外将是 使用鼠标模型在体内确认。申请人提出这些数据 研究应产生有关膀胱调节的宝贵信息 上皮增殖和IC的发病机理。