Urinary Biomarkers of Lower Urinary Traxct Symptoms (LUTS) in Men

这个项目的目标是召集一个跨学科的研究团队来检验这一假设 尿液代谢和蛋白质组生物标志物可预测人类下尿路治疗的疗效 为下尿路症状(LUTS)的机制研究确定最合适的动物模型。当前 数据与人类LUTS有多种病因和多种症状的观点最为一致。 LUTS的可能病因包括，但不限于，良性前列腺增生症，炎症性前列腺癌 前列腺和膀胱颈、前列腺和膀胱颈的肌张力变化与神经学 下尿路的变化。理想情况下，LUT的治疗将考虑到不同的 针对疾病的具体表现，实现对个别患者更快速有效的治疗。障碍： 实现这一目标包括缺乏足够的生物标记物来区分人类的不同表现 LUT和缺乏关于最合适的动物模型的机制研究的清晰度 LUT的不同表现。为了消除在外地取得进展的这些障碍，该项目将进行 实验被组织成三个具体目标。目标1将使用以下方法识别人类LUTS的尿液生物标记物 蛋白质组学和代谢组学方法。目标2将确定相关生物标记物表达的变化 有效治疗LUTS症状。目标3将进行物种间比较研究，以确定 人类LUTS患者、细菌性前列腺炎小鼠和激素诱导的小鼠之间的生物标志物相似性 尿路梗阻。预计完成这些目标将识别出能够 将LUT分成不同的疾病亚型，预测治疗反应，并识别 最适合于研究与不同子类型的 LUTS。完成这些目标还将创建支持更多 利用人类患者确定下尿路综合征(S)根本原因的综合跨学科方案 数据和来自具有不同尿路疾病表现的动物模型的数据。

The goal of this project is to bring together an interdisciplinary team of researchers to test the hypothesis that urine metabolic and proteomic biomarkers can predict the response to therapy for human lower urinary tract symptoms (LUTS) and identify the most appropriate animal models for mechanistic studies of LUTS. Current data are most consistent with the idea that human LUTS has multiple etiologies and multiple manifestafions. Plausible etiologies for LUTS include, but are not limited to, benign prostatic hyperplasia, inflammafion in the prostate and bladder neck, changes in smooth muscle tone in the prostate and bladder neck, and neurologic changes in the lower urinary tract. Ideally, treatment for LUTS would take into account the different manifestations of disease to achieve more rapid and effecfive therapy for individual patients. Barriers to achieving this goal include the lack of adequate biomarkers to stratify the different manifestations of human LUTS and a lack of clarity regarding the most appropriate animal models for mechanistic studies ofthe different manifestations of LUTS. To address these barriers to progress in the field, this project will conduct experiments organized into three Specific Aims. Aim 1 will identify urine biomarkers of human LUTS using proteomic and metabolomic approaches. Aim 2 will identify changes in biomarker expression that correlate with effective treatment of LUTS symptoms. Aim 3 will conduct interspecies comparative studies to identify biomarker similarities among human LUTS patients, mice with bacterial prostatitis, and mice with hormoneinduced urinary obstrucfion. It is anticipated that completion of these Aims will identify biomarkers that can stratify LUTS into different disease sub-types, predict response to therapy, and identify animal models that are most appropriate for investigating the underlying mechanisms associated with different sub-types of LUTS. Completion of these Aims will also create a base of knowledge needed to support a more comprehensive interdisciplinary project to determine the underiying cause(s) of LUTS using human patient data and data from animal models with different manifestations of urinary tract disease.