Molecular signatures associated with prostatic inflammation in rodent models.

啮齿动物模型中与前列腺炎症相关的分子特征。

• 批准号: 8566145
• 负责人: Zhou Wang
• 金额: $ 24.67万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-28 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8566145
• 关键词: ATP Receptors; Advisory Committees; Affect; Afferent Neurons; Androgen Receptor; Androgens; Animal Model; Award; Benign; Benign Prostatic Hypertrophy; Bladder; Bladder Dysfunction; Capsaicin; Characteristics; Collaborations; Communities; Complex; Disease; Dose; Elderly man; Endocrinology; Epithelial; Epithelial Cells; Formalin; Formalin Tests; Functional disorder; Funding; Future; Gene Expression; Genes; Homeostasis; Human; Inflammation; Inflammatory; Injection of therapeutic agent; Interdisciplinary Study; Lead; Medical; Mesenchymal; Modeling; Molecular; Molecular Analysis; Molecular Profiling; P2X-receptor; Pathogenesis; Pathology; Pharmacology; Physiological; Prevention; Preventive; Production; Prostate; Prostatic; Prostatic Tissue; Rattus; Research; Research Personnel; Research Project Grants; Resources; Rodent; Rodent Model; Role; Signal Pathway; Societies; Specimen; TNFRSF5 gene; Testing; Testosterone; Therapeutic; Tissues; Universities; Up-Regulation; Urination; Urine; Urology; Work; aged; chemokine; clinically significant; cost; cytokine; lower urinary tract symptoms; men; multidisciplinary; novel; programs; research study; success

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.

匹兹堡大学跨学科规划中心（University of Pittsburgh Planning Center for Interdisciplinary 良性泌尿学研究（IR-BU）旨在研究“与前列腺相关的分子特征”， 啮齿动物模型中的炎症”。由于炎症在BPH中的重要性，一组研究人员 包括内分泌学，病理学，泌尿学和药理学在内的不同专业知识将共同努力， 确定炎症诱导的分子和细胞变化的相似性和不同性，和/或 在这个多学科的项目中，啮齿动物和人类之间的前列腺外。研究假设 前列腺炎症可以诱导与人类BPH相关的分子和细胞变化。这 在当前的资助期内，福尔马林诱导的低等级 炎症增强福尔马林注射大鼠前列腺模型中雄激素应答基因的表达 和我们之前的发现，雄激素反应基因的表达在人类BPH上皮细胞中升高， 细胞以福尔马林诱导的大鼠前列腺炎症为模型，我们建议确定 前列腺炎症对膀胱和传入功能的影响（具体目标1）， 前列腺和尿液（具体目标2）和前列腺上皮-间质转化（具体目标3）。的 这项研究项目的成功将确定啮齿动物中的相关靶点和信号通路， 导致前列腺组织稳态改变，这是人类BPH的特征。 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提供强有力的行政支助， 合作和教育丰富。核心还将负责分配和监督 IR-BU资源。通过支持教育充实和研究项目， 核心将有助于既整合IR-BU到大学社区作为一种资源， 吸引新的研究人员进入BPH领域。