University of Pittsburgh Planning Center for Benign Prostate Hyperplasia Research

描述（由申请人提供）：本申请来自匹兹堡大学良性泌尿科跨学科研究规划中心（IR-BU），旨在研究“啮齿动物和人类前列腺炎症和抗炎症相关的分子特征”。通过拟议的多学科项目，一组具有不同专业知识的研究人员，包括内分泌学，病理学，泌尿学和药理学，将共同努力，确定炎症诱导的基因表达变化在啮齿动物和人类前列腺之间的异同。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tgf - β）信号通路的影响，因为它们在BPH发病机制中已确定或涉及的作用。研究假设，炎症在啮齿动物和人类中对雄激素反应基因、炎症细胞因子和tgf - β的水平和下游靶点产生相似的影响。以辣椒素致大鼠前列腺急性和细菌性慢性炎症为模型。我们将比较啮齿动物和人类前列腺中雄激素反应性基因表达（Specific Aim 1）、炎症反应（Specific Aim 2）和tgf - β信号（Specific Aim 3）的炎症相关改变。该研究项目的成功将确定啮齿动物对炎症反应的相关靶点和信号通路，从而改变前列腺组织的稳态，这是人类前列腺增生的特征。

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.