# Molecular mechanisms of initiation of benign prostatic hyperplasia

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $578,825

## Abstract

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.

## Key facts

- **NIH application ID:** 10102231
- **Project number:** 5R01DK107436-06
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Li Xin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $578,825
- **Award type:** 5
- **Project period:** 2016-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102231

## Citation

> US National Institutes of Health, RePORTER application 10102231, Molecular mechanisms of initiation of benign prostatic hyperplasia (5R01DK107436-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10102231. Licensed CC0.

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