University of Pittsburgh Planning Center for Benign Prostate Hyperplasia Research

描述(申请人提供)：这份由匹兹堡大学良性泌尿外科跨学科研究规划中心(IR-BU)提出的申请是为了研究“与啮齿动物和人类的前列腺炎症和抗炎相关的分子标记”。通过拟议的多学科项目，一个具有不同专业知识(包括内分泌学、病理学、泌尿学和药理学)的研究团队将共同努力，确定啮齿动物和人类前列腺之间炎症诱导的基因表达变化的异同。我们将特别分析炎症对内分泌(即雄激素)和旁分泌(即细胞因子和转化生长因子-β)信号通路的影响，以确定它们在BPH发病机制中的既定或牵连作用。研究假设是，炎症在啮齿类动物和人类身上对雄激素反应基因以及炎症细胞因子和转化生长因子-β的水平和下游靶点产生了类似的影响。以辣椒素诱导的大鼠前列腺急性炎症和细菌感染诱导的慢性炎症为模型。我们将比较在啮齿动物和人类前列腺中与炎症相关的雄激素反应基因表达(特异性目标1)、炎症反应(特异性目标2)和转化生长因子-β信号(特异性目标3)的变化。该研究项目的成功将在啮齿类动物中确定相关的靶点和信号通路，这些啮齿动物对炎症做出反应，以产生人类BPH特有的改变的前列腺组织稳态。 IR-BU建立了一个行政核心，其中包括一个执行委员会和一个内部咨询委员会，将通过项目审查、促进合作和教育丰富提供强有力的行政支持。核心还将负责IR-BU资源的分配和监督。通过支持教育丰富和研究项目，行政核心将有助于通过将IR-BU作为资源纳入大学社区，并吸引新的研究人员进入良性前列腺增生症领域。 公共卫生相关性：良性前列腺增生症(BPH)/下尿路症状(LUTS)是影响大多数老年男性的主要医疗问题，每年造成社会约40亿美元的损失。拟议的多学科研究的成功将有助于进一步分析BPH的分子机制。

DESCRIPTION (provided by applicant): This application from the University of Pittsburgh Planning Center for Interdisciplinary Research in Benign Urology (IR-BU) is proposed to study "Molecular signatures associated with prostatic inflammation and antiinflammation in rodents and humans". Through the proposed multidisciplinary project, a team of investigators with different expertise including endocrinology, pathology, urology, and pharmacology will work together to determine similarities and dissimilarities in inflammation-induced gene expression changes between rodent and human prostates. We will particularly assay the impact of inflammation on the endocrine (i.e. androgens) and paracrine (i.e. cytokines and TGF-beta) signaling pathways given their established or implicated roles in BPH pathogenesis. The research hypothesis is that inflammation exerts similar effects in rodents and humans on androgen responsive genes and the levels and downstream targets of inflammatory cytokines and TGF-beta. Capsaicin-induced acute and bacterial infection-induced chronic inflammation in the rat prostate will be used as models. We will compare inflammation-associated alterations in androgen-responsive gene expression (Specific Aim 1), inflammatory responses (Specific Aim 2), and TGF-beta signaling (Specific Aim 3) in the rodent and human prostates. The success of this research project will identify relevant targets and signaling pathways in rodents that respond to inflammation to generate altered prostate tissue homeostasis characteristic of BPH in humans. The IR-BU has established an Administrative Core, which includes an Executive Committee and an Internal Advisory Committee, will provide strong administrative support through project review, promoting collaborations, and educational enrichment. The Core will also be responsible for allocation and oversight of IR-BU resources. Through supporting the educational enrichment and research project, the Administrative Core will help to both integrate the IR-BU into the University community by serving as a resource and to attract new investigators to the field of BPH. PUBLIC HEALTH RELEVANCE: Benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) is a major medical problem affecting most elderly men and costing society ~$4 billion annually. Success of the proposed multidisciplinary research will facilitate further analysis of the molecular mechanisms of BPH.