Cellular and molecular mediators of fibrosis in the development of urinary tract dysfunction

尿路功能障碍发展过程中纤维化的细胞和分子介质

基本信息

批准号：
10331481
负责人：
WILLIAM A RICKE
金额：
$ 3.52万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-24 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10331481
关键词：
Adverse effects Affect Animals Benign Biomedical Research Bladder Boston Breeding Cell Lineage Cells Cheese Clinical Collaborations Collagen Communication Communities Computer software Consensus Consequentialism Data Databases Development Diagnosis Educational process of instructing Elderly Environment Estrogen Receptor alpha Etiology FDA approved Fibroblasts Fibrosis Financial Support Fostering Freezing Frozen Semen Functional Magnetic Resonance Imaging Functional disorder Funding Future Genetic Transcription Goals Health Care Costs Histologic Human Image Impairment Inflammation Inflammatory Infrastructure Insignia Institution Interleukin-13 Interleukin-4 Investigation Lead Leadership Learning Lobster Lower urinary tract Maps Mediator of activation protein Medical Metadata Methods Molecular Molecular Target Mouse Strains Mus Myofibroblast Pathway interactions Physicians Physiology Pre-Clinical Model Process Proliferating Prostate Prostatic Prostatic Tissue Protocols documentation Publications Quality of life Reproducibility Research Research Personnel Research Project Grants Resistance Resources SECTM1 gene SRD5A2 gene Sampling Scientific Advances and Accomplishments Scientist Smooth Muscle Solid Source Specimen Steroids Stream Stromal Cells Sum Symptoms Testing Testosterone 5-alpha-Reductase Therapeutic Tissues Training Ultrasonography Urethra Urinary tract Urination Urine Urology Vision Voice Work analytical method biobank connective tissue growth factor contrast enhanced data dissemination data sharing design experience imaging modality improved in vivo inhibitor/antagonist innovation lower urinary tract symptoms male member men mouse model novel therapeutics pre-clinical preclinical study programs radiological imaging searchable database single-cell RNA sequencing synergism tissue resource tool undergraduate research experience undergraduate student urinary urologic web site

Adverse effects Affect Animals Benign Biomedical Research Bladder Boston Breeding Cell Lineage Cells Cheese Clinical Collaborations Collagen Communication Communities Computer software Consensus Consequentialism Data Databases Development Diagnosis Educational process of instructing Elderly Environment Estrogen Receptor alpha Etiology FDA approved Fibroblasts Fibrosis Financial Support Fostering Freezing Frozen Semen Functional Magnetic Resonance Imaging Functional disorder Funding Future Genetic Transcription Goals Health Care Costs Histologic Human Image Impairment Inflammation Inflammatory Infrastructure Insignia Institution Interleukin-13 Interleukin-4 Investigation Lead Leadership Learning Lobster Lower urinary tract Maps Mediator of activation protein Medical Metadata Methods Molecular Molecular Target Mouse Strains Mus Myofibroblast Pathway interactions Physicians Physiology Pre-Clinical Model Process Proliferating Prostate Prostatic Prostatic Tissue Protocols documentation Publications Quality of life Reproducibility Research Research Personnel Research Project Grants Resistance Resources SECTM1 gene SRD5A2 gene Sampling Scientific Advances and Accomplishments Scientist Smooth Muscle Solid Source Specimen Steroids Stream Stromal Cells Sum Symptoms Testing Testosterone 5-alpha-Reductase Therapeutic Tissues Training Ultrasonography Urethra Urinary tract Urination Urine Urology Vision Voice Work analytical method biobank connective tissue growth factor contrast enhanced data dissemination data sharing design experience imaging modality improved in vivo inhibitor/antagonist innovation lower urinary tract symptoms male member men mouse model novel therapeutics pre-clinical preclinical study programs radiological imaging searchable database single-cell RNA sequencing synergism tissue resource tool undergraduate research experience undergraduate student urinary urologic web site

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项目摘要

PROJECT SUMMARY- OVERALL No consequential advances in medical treatment of prostate-related lower urinary tract symptoms (LUTS) have emerged in decades. Existing medical therapies improve LUTS but robustness of these effects are marginal. Not all men respond to existing therapies, some respond with adverse effects requiring discontinuation of therapy, and most experience a progressive worsening of symptoms pursuant to initial relief. Multiple mechanisms drive development and progression of prostate-related LUTS. The overarching goal of the O’Brien Center for Benign Urology Research is to identify mechanisms that result in lower urinary tract dysfunction and prostate-related LUTS. The overarching hypothesis of the center is that fibrosis is a cause of male LUTS. In contrast to benign prostatic enlargement and smooth muscle dysfunction, prostatic fibrosis remains untargeted by existing therapies. In order to advance the scientific understanding and medical management of prostatic fibrosis, it will be necessary to: (1) identify cellular and molecular mediators of fibrosis and therapeutically- susceptible pathways using clinical specimens, (2) develop and validate preclinical mouse models of prostatic fibrosis and strategies for granular assessment of voiding function, (3) test new therapies in these preclinical models with the long term goal of treating fibrosis in men, and (4) develop new non-invasive radiologic imaging strategies with the long-term goal of diagnosing prostatic fibrosis in men. Two additional goals will advance the urologic research community: (1) develop and publicly disseminate resources to increase research efficiency, reproducibility, and rigor, and (2) cultivate an outstanding educational enrichment program to attract and retain young basic- and physician-scientists into the benign urologic research field. The Center will apply state of the art molecular and histological methods to visualize and characterize fibrosis in a range of human and animal prostatic tissues and examine how prostatic fibrosis develops, progresses, and responds to treatment. Interactions and engagement with the O’Brien Centers’ Interaction Core, the UW O’Brien Centers Website, and GUDMAP will accelerate the dissemination of data, software, methods, and tissue resources to the greater biomedical community. The leadership and experience within the Center will allow for the promotion of interactions among Center Projects, the Biomedical Research Core, and other Centers (U54, P20, K12) through communication, collaboration, and coordination. The larger vision is that O’Brien Centers will be a nidus for ideas, research, resources, training, and a unified voice across the urologic research community. To realize this vision, the Centers must become more than the sum of their parts. The UW O’Brien Center and its affiliates will contribute to this synergism by leveraging existing Center assets and relationships, conducting rigorous investigation, fostering teaching and learning, and through vigorous pursuit of innovation. With the solid financial support and “buy-in” from UW and its affiliates, Core A will lead this vision for this O’Brien Center.

项目摘要总体前列腺相关的下尿路症状（LUTS）的医学治疗中没有结果的进展几十年来出现。现有的医疗疗法改善了LUTS，但这些影响的鲁棒性是微不足道的。并非所有男人都对现有疗法做出反应治疗，大多数人会根据最初的缓解感到遗憾。多种的机制推动了与前列腺相关LUTS的发展和进展。奥布莱恩的总体目标良性泌尿外科研究中心是确定导致尿路功能障碍和前列腺相关的LUTS。该中心的总体假设是纤维化是雄性LUT的原因。在与良性前列腺扩张和平滑肌功能障碍形成鲜明对比，前列腺纤维化仍未定位通过现有疗法。为了促进前列腺的科学理解和医学管理纤维化，必须：（1）确定纤维化和治疗的细胞和分子介质使用临床标本的易感途径，（2）开发和验证前列腺的临床前小鼠模型纤维化和粒状评估空隙功能的策略，（3）测试这些临床前的新疗法具有治疗男性纤维化的长期目标的模型，以及（4）开发新的非侵入性放射学成像男性诊断性前列腺纤维化的长期目标的策略。额外的两个目标将推进泌尿科研究社区：（1）开发并公开传播资源以提高研究效率，可重复性和严格性，以及（2）培养一个出色的教育丰富计划，以吸引和保留年轻的基本和身体科学家进入良性泌尿科研究领域。该中心将采用艺术分子和组织学方法可视化和表征一系列人类和动物的纤维化前列腺组织并检查前列腺纤维化的发展，进展和对治疗的反应。与O'Brien Centers的互动核心，UW O'Brien Centers网站和 GudMap将加速数据，软件，方法和组织资源的传播生物医学界。中心内的领导和经验将允许促进中心项目之间的互动，生物医学研究核心以及其他中心（U54，P20，K12）通过沟通，协作和协调。更大的愿景是，奥布莱恩中心将成为整个泌尿科研究界的思想，研究，资源，培训和统一的声音。意识到这一点视觉，中心必须成为其各个部分的总和。 UW O’Brien Center及其分支机构将通过利用现有的中心资产和人际关系来促进这种协同作用调查，促进教学，并通过猛烈的追求创新。与坚实的财务 UW及其分支机构的支持和“买入”，Core A将为这个O'Brien中心带来这一愿景。