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

描述(申请人提供)：这个项目的目标是聚集一个跨学科的研究团队，测试尿液代谢和蛋白质组生物标记物可以预测人类下尿路症状(LUTS)治疗反应的假设，并为LUTS的机制研究确定最合适的动物模型。目前的数据最符合人类LUTS有多种病因和多种表现的观点。LUTS的可能病因包括但不限于良性前列腺增生、前列腺和膀胱颈的炎症、前列腺和膀胱颈的平滑肌张力改变以及下尿路的神经改变。理想情况下，LUTS的治疗将考虑到疾病的不同表现，以实现对个别患者更快速和有效的治疗。实现这一目标的障碍包括缺乏足够的生物标志物来对人类LUT的不同表现进行分层，以及对于用于LUT不同表现的机制研究的最合适的动物模型缺乏透明度。为了解决在这一领域取得进展的这些障碍，该项目将进行组织成三个具体目标的实验。目的1利用蛋白质组学和代谢组学方法鉴定人LUTS的尿液生物标记物。目的2将确定与LUTS症状有效治疗相关的生物标记物表达的变化。目的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尿路梗阻小鼠之间的生物标志物相似性。预计这些目标的完成将识别生物标志物，这些生物标志物可以将LUT分成不同的疾病亚型，预测治疗反应，并识别最适合研究与不同亚型LUT相关的潜在机制的动物模型。这些目标的完成还将为支持一个更全面的跨学科项目奠定必要的知识基础，该项目使用人类患者数据和具有不同尿路疾病表现的动物模型的数据来确定下尿路综合征的潜在原因(S)。

DESCRIPTION (provided by applicant): 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 manifestations. Plausible etiologies for LUTS include, but are not limited to, benign prostatic hyperplasia, inflammation 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 effective 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 of the 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 hormone-induced urinary obstruction. 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 underlying cause(s) of LUTS using human patient data and data from animal models with different manifestations of urinary tract disease.