Molecular signatures associated with prostatic inflammation in rodent models.

描述(由申请人提供)：匹兹堡大学良性泌尿外科跨学科研究规划中心(IR-BU)提出的这份竞争性续签申请是为了研究“与啮齿动物模型中的前列腺癌炎症相关的分子签名”。由于炎症在BPH中的重要性，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，在这个多学科项目中确定啮齿动物和人类之间由炎症诱导的前列腺内外分子和细胞变化的异同。研究假设是前列腺炎症可以诱导与人类BPH相关的分子和细胞变化。支持这一假说的是，在目前的资助期间，福尔马林诱导的低度炎症增强了福尔马林注射大鼠前列腺模型中雄激素反应基因的表达，以及我们之前的发现，在人BPH上皮细胞中雄激素反应基因的表达增加。以福尔马林诱导的大鼠前列腺炎症为模型，我们提出了前列腺炎症对膀胱和传入功能的影响(特异靶1)、前列腺炎性细胞因子在前列腺和尿液中的分布(特异靶2)以及前列腺上皮-间充质转化(特异靶3)。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。

DESCRIPTION (provided by applicant): This competing renewal 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 in rodent models". Because of the importance of inflammation in BPH, a team of investigators with different expertise including endocrinology, pathology, urology, and pharmacology will work together to determine similarities and dissimilarities in inflammation-induced molecular and cellular changes in and/or outside the prostate between rodents and humans in this multidisciplinary project. The research hypothesis is that prostatic inflammation can induce molecular and cellular changes associated with human BPH. This hypothesis is supported by the finding during the current funding period that formalin-induced low grade inflammation enhanced expression of androgen-responsive genes in the formalin-injection rat prostate model and our previous finding that androgen-responsive gene expression is elevated in human BPH epithelial cells. Using formalin-induced rat prostate inflammation as a model, we propose to determine the effect of prostatic inflammation on bladder and afferent function (Specific Aim 1), inflammatory cytokine profile in the prostate and urine (Specific Aim 2), and prostatic epithelial-mesenchymal transition (Specific Aim 3). 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.