Urine Antiproliferative Peptide in Interstitial Cystitis

间质性膀胱炎中的尿液抗增殖肽

• 批准号: 6635081
• 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 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635081
• 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（改编自申请人摘要）：间质性膀胱炎（IC） 是一种慢性膀胱疾病，通常会对患者的生活产生破坏性影响， 在美国大约有45万人。IC的病因不明， 目前没有可靠有效的治疗方法。因此重要的是 继续寻找这种使人衰弱的疾病的原因， 系统地设计有效的治疗方法。 申请人报告发现了两个具体而显著的异常 与对照组相比，IC患者的尿液中存在，这可能与 这种疾病的发病机制-存在低分子量尿 体外抑制膀胱上皮细胞增殖的肽 （抗增殖因子，或APF）和复杂的变化水平， 特异性尿上皮细胞生长因子，包括显著 肝素结合表皮生长因子样生长的尿液水平降低 因子因为受损的膀胱上皮是IC的中心发现，所以它是 APF和生长因子异常可能直接参与 这种疾病的发病机制。 拟议的研究旨在确定APF的机制 调节膀胱上皮细胞增殖。此外，具体影响 HPLC纯化的APF对体外膀胱上皮细胞生理学的影响 使用小鼠模型在体内证实。申请人建议这些数据 研究应该产生关于膀胱调节的有价值的信息， 上皮细胞增殖和IC的发病机制。