Identifying the role of lipid accumulation and foam cells in benign prostate disease - PROJECT SUMMARY/ABSTRACT Benign prostatic pathological changes (collectively known as Benign Prostatic Hyperplasia/BPH), characterized by lower urinary tract symptoms (LUTS), is a prevalent condition that significantly impacts the quality of life in aging males. Current medical treatments for LUTS/BPH are largely ineffective, necessitating a deeper understanding of the underlying pathogenesis to develop novel therapeutic strategies. Our prior investigation identified that lipid accumulates in the prostate in BPH as well as macrophages enter the prostate lumen and become lipid-laden foam cells. However, we have very limited information on the etiology and consequences of these processes. Therefore, through the utilization of clinical specimens, a well-established mouse model of prostatic disease, and the creation and testing of novel mouse models, we will investigate the intricate interplay between prostatic inflammation, lipid accumulation and urinary dysfunction. Accordingly, aim 1 will elucidate the role of CXCL17 as an epithelia-derived cytokine in remodeling the prostatic immune environment in mice as well as will identify candidate cytokines that drive the same process in humans via a comprehensive transcriptomic and proteomic approach. Aim 2 will generate a mouse model with inducible upregulation in lipid synthesis pathways in the prostate epithelium to assess pathological and functional consequences. Aim 3 will decipher the impact of foam cell-derived factors via transurethral instillation. Our research team consists of experts in urology, immunology, and proteomics research, ensuring a comprehensive and multi-faceted approach to address the research questions. The anticipated outcomes of this research project include a better understanding of the pathogenesis of LUTS, the identification of novel biomarkers for disease diagnosis and monitoring, and the development of innovative therapeutic strategies targeting foam cell formation and lipid accumulation. In conclusion, this study holds significant promise for advancing our understanding of benign prostate disease and ultimately improving clinical outcomes for patients suffering from lower urinary tract symptoms. By elucidating the role of lipid accumulation and foam cells, we aim to pave the way for the development of effective interventions to alleviate the burden of LUTS in the aging male population.
