# Fibroblast subsets in BPH pathogenesis

> **NIH NIH U54** · STANFORD UNIVERSITY · 2023 · $332,116

## Abstract

ABSTRACT – PROJECT 1
Benign Prostatic Hyperplasia (BPH) is the benign enlargement of the prostate gland that occurs in older men,
obstructing bladder outflow. The resultant lower urinary tract symptoms, such as urgency, frequency and
incomplete emptying, have considerable morbidity, and carry annual healthcare costs in the Billions. Current
BPH treatments are not very effective because the drugs target normal prostate physiology but not BPH
pathophysiology, which is still poorly understood. New disease-targeted therapies will require a more detailed
knowledge of BPH pathogenesis. In genomic studies of BPH clinical samples, we discovered a stromal gene
signature that correlated with BPH symptoms, and an enrichment of fibroblasts overexpressing signaling
proteins BMP5 and CXCL13. Fibroblast BMP5 enhanced prostate epithelial proliferation and drove gene
expression profiles to mimic BPH tissue. From these data, we hypothesize that BPH is driven (at least in part)
by pathogenic fibroblast cell subset(s), where defining those subsets will provide important new opportunities
for disease targeted therapies. Towards that goal, the proposed studies aim to Define the fibroblast subsets in
BPH versus normal prostate; Determine the key interactions between BPH fibroblast subsets and prostate
epithelium that drive prostate enlargement; and Distinguish between BPH origins in embryonic re-awakening
versus injury response. Study findings will provide new understanding of the contribution of prostate stroma to
BPH pathogenesis, and identify new strategies for targeted treatment.

## Key facts

- **NIH application ID:** 10690585
- **Project number:** 5U54DK130065-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JONATHAN R POLLACK
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $332,116
- **Award type:** 5
- **Project period:** 2021-09-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690585

## Citation

> US National Institutes of Health, RePORTER application 10690585, Fibroblast subsets in BPH pathogenesis (5U54DK130065-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10690585. Licensed CC0.

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