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Osteopontin: A Novel Mediator of prostatic inflammation and fibrosis

骨桥蛋白：前列腺炎症和纤维化的新型介质

基本信息

批准号：
10326391
负责人：
PETRA POPOVICS
金额：
$ 6.53万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-15 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10326391
关键词：
3-Dimensional Age Aging Animal Model Area Autoimmune Benign Biological Assay Biomedical Engineering Bladder CD8-Positive T-Lymphocytes CXCL1 gene Cancer Biology Cell Communication Chronic Clinical Coculture Techniques Collagen Data Deposition Detection Development Disease Progression Economic Burden Endocrinology Environment Epithelial Estradiol Extracellular Matrix Familiarity Fibronectins Fibrosis Functional disorder Funding Genetic Goals Healthcare Systems IL6 gene Immune Immune response Implant In Vitro Inflammation Inflammatory Institutes Institution Kidney Knockout Mice Knowledge Link Lower urinary tract Mediating Mediator of activation protein Medical Mentors Methods Modeling Molecular Molecular Biology Molecular Target Mus Organ Pathology Pathway interactions Pharmacology Phosphoproteins Physiological Process Prostate Prostatic Prostatic Diseases Prostatic Tissue Proteins Quality of life Recovery Reporting Research Research Personnel Research Proposals Role Secondary to Signal Transduction Stream Stromal Cells Symptoms Technology Testing Testosterone Tissue Engineering Tissues Training Urination Urology Uropathogenic E. coli Vocational Education autoimmune inflammation base career career development chemokine clinically significant common symptom cost cytokine design drug development immunopathology improved in vitro Model in vivo in vivo Model lower urinary tract symptoms male men monolayer new therapeutic target novel novel diagnostics novel therapeutics osteopontin overexpression programs prostatitis public health relevance research and development skills steroid hormone subcutaneous targeted treatment urinary

项目摘要

PROJECT SUMMARY/ABSTRACT The overarching goal of my proposal is to acquire technical and professional skills to become an independent investigator at a leading academic institution and develop a research program deciphering the molecular mechanism of inflammation induced prostatic tissue remodeling and fibrosis. This will be pursued through a scientific project that will determine whether osteopontin, a pro-fibrotic secreted phosphoprotein, stimulates prostatic inflammation, fibrosis, and lower urinary tract dysfunction. My training is focused on four key areas: 1) functional testing of mouse urinary function, 2) developing biomedical engineering technologies to study prostatic fibrosis in vitro, 3) testing and further developing animal models to study inflammation-induced prostatic fibrosis and its consequences on urinary function and, 4) gaining essential training in immune-regulated tissue remodeling. UW-Madison and the UW O`Brien Center for Benign Urology Research presents a unique environment for the proposed research and career development activities. This includes seminars presented by local and national leaders of the field, career development activities of several institutes across campus, clinical training of the Department of Urology, and specific training in immunopathology and tissue engineering. Lower urinary tract symptoms (LUTS) secondary to benign prostatic diseases deteriorate the quality of life as men age. The treatment of male LUTS costs $4 billion annually and presents an economic burden on our healthcare system. It has been recently identified that prostatic inflammation and fibrosis are associated with LUTS, but the exact contribution of these mechanism to urinary dysfunction is unknown. Medical therapies targeting inflammation and fibrosis could enhance drug development and provide novel molecular targets for LUTS. Based on my preliminary studies, I hypothesize that inflammation-induced osteopontin levels stimulate prostatic fibrosis and lower urinary tract dysfunction (LUTD). The hypothesis will be tested by the following aims: 1) Test the hypothesis that OPN is required for inflammation-induced prostatic collagen accumulation and LUTD, 2) Test the hypothesis that OPN induces prostatic fibrosis. The proposal will provide novel detection of collagen deposition, 3D in vitro and in vivo models of prostatic fibrosis. It will also decipher the specific role of inflammation-induced prostatic fibrosis in lower urinary tract dysfunction. This will be achieved by capitalizing on recently established prostatic inflammation models and state-of-the-art urinary physiological tests uniquely available at the UW-Madison.

项目总结/文摘