Molecular signatures associated with prostatic inflammation in rodent models.

描述（由申请人提供）：这是匹兹堡大学良性泌尿科跨学科研究规划中心（IR-BU）提出的竞争性更新申请，旨在研究“啮齿动物模型中与前列腺炎症相关的分子特征”。由于炎症在前列腺增生中的重要性，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，在这个多学科项目中确定啮齿动物和人类前列腺内外炎症诱导的分子和细胞变化的异同。研究假设前列腺炎症可以诱导与人类前列腺增生有关的分子和细胞变化。这一假设得到了以下研究结果的支持：在注射福尔马林的大鼠前列腺模型中，福尔马林诱导的低级别炎症增强了雄激素应答基因的表达，以及我们之前发现的雄激素应答基因在人前列腺增生上皮细胞中的表达升高。以福尔马林诱导的大鼠前列腺炎症为模型，我们拟确定前列腺炎症对膀胱和传入功能的影响（Specific Aim 1），前列腺和尿液中的炎症细胞因子谱（Specific Aim 2），以及前列腺上皮-间质转化（Specific Aim 3）。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 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.