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Molecular mechanisms of initiation of benign prostatic hyperplasia

良性前列腺增生起始的分子机制

基本信息

批准号：
10398260
负责人：
Li Xin
金额：
$ 57.77万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10398260
关键词：
AXIN2 gene Acute Affect Age Aging Anatomy Attenuated Bacterial Infections Benign Prostatic Hypertrophy Biological Cells Development Disease Embryo Epithelial Epithelial Cell Proliferation Epithelial Cells Epithelial-Stromal Communication Etiology Fibroblast Growth Factor Gene Expression Genetically Engineered Mouse Goals Growth Heterogeneity Histologic Homeostasis Human In Situ In Vitro Inflammation Left Life Ligands Mesenchymal Mitotic Molecular Mus Muscle Nodule Non-Malignant Pathogenesis Peptide Initiation Factors Phenotype Play Process Prostate Prostatic Prostatic Epithelium Prostatic duct Quantitative Reverse Transcriptase PCR RNA Role Signal Transduction Specimen Stromal Cells Stromal Hyperplasia Techniques Tissues Transforming Growth Factor beta Urethra Urinary Retention WNT Signaling Pathway Work autocrine base beta catenin cohort epithelial stem cell fetal improved in vitro Assay in vivo insight laser capture microdissection lower urinary tract symptoms men mouse model novel novel therapeutics paracrine single-cell RNA sequencing stem cells theories transcriptome sequencing

项目摘要

Project Summary/Abstract Benign prostatic hyperplasia (BPH) is a progressive condition in aging men that is characterized by the enlargement of the periurethral regions of the prostate gland. An estimated 50% of men have histologic evidence of BPH by age 50 years and 75% by age 80 years. BPH is often accompanied by lower urinary tract symptoms (LUTS). BPH is rarely fatal, but may cause serious life-threatening complications such as acute urinary retention if left untreated. However, molecular mechanisms of BPH initiation and progression remain incompletely understood. The lack of understanding of these mechanisms is a barrier to improved treatment. BPH is a heterogeneous disease that results from nonmalignant proliferations of both the prostate epithelial and stromal compartments. The stromal nodules and the epithelial glandular nodules are the two typical nodules in BPH. Histological comparison of the stromal nodules with human fetal prostate stroma revealed that the ontogenetic processes of fetal prostate stroma (a transition from immature mesenchymal phenotype to fibroblastic, fibromuscular, and ultimately smooth-muscular phenotype) are recapitulated in the development of the BPH stromal nodules. This observation supports a theory of embryonic “reawakening”, which proposes that improper reactivation of embryonic signaling like FGFs attributes to initiation and progression of these stromal nodules. Formation of glandular nodules is suggested to develop as a result of stromal hyperplasia and deregulated stromal-epithelial interaction. But the underlying molecular mechanisms for glandular nodules have not been defined definitively. Our preliminary study shows that the Wnt signaling is active in prostate stromal cells and is capable of regulating the prostate epithelial stem cell activity. The goal of this application is to use a combination of molecular and cellular biological approaches, genetically engineered mouse models, and human BPH specimens to investigate how the Wnt signaling in prostate stromal cells is altered in BPH and how it affects BPH pathogenesis.

项目总结/文摘