# CTGF drives voiding dysfunction through expression of collagen in periurethral SRD5A2+ fibroblasts

> **NIH NIH U54** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $141,743

## Abstract

PROJECT SUMMARY- PROJECT 2
Lower urinary tract symptoms cost more than $4 billion annually. Though current medical therapies reduce
prostate volume and relax smooth muscle to address symptoms, existing therapies are not curative. Three things
are clear: (1) male lower urinary tract symptoms derive from multiple underlying pathologies, not just prostatic
enlargement or muscle dysfunction (2) current therapies do not effectively target pathologies outside of benign
enlargement and smooth muscle dysfunction, and (3) there is a need to identify additional mechanisms
underlying lower urinary tract symptom etiology to formulate therapies that are more effective. The overarching
goal of the O’Brien Center for Benign Urology Research is to identify mechanisms that result in lower urinary
tract dysfunction and prostate-related lower urinary tract symptoms (LUTS). Prostatic collagen accumulation
(fibrosis) has been identified as a cause of male lower urinary tract symptoms. Prostatic collagen accumulation
has been linked to prostatic stiffness, lower urinary tract symptoms, and failed medical treatment. It will not be
possible to treat prostatic fibrosis and associated voiding dysfunction until prostatic collagen-producing cells are
identified. The goal of this project is to tackle this challenge by pinpointing the cellular and molecular origins of
pathological collagen production in the prostate.
A subpopulation of human prostatic fibroblasts residing in close proximity to the urethra and expressing steroid
five alpha reductase type II (SRD5A2) has been identified, supporting the central hypothesis that inflammation
causes these fibroblasts to proliferate, synthesize connective tissue growth factor (CTGF) and produce collagen.
Collagen accumulation in turn leads to urethral stiffening, bladder outlet obstruction, urinary retention, and
voiding dysfunction. The proposed studies offers essential insight into the pathogenesis of prostatic fibrosis, a
mechanism of lower urinary tract symptom medical therapy failure. Aim 1 will test the hypothesis that
inflammation increases human prostatic SRD5A2+ fibroblast frequency and drives CTGF and COL1A2
expression. Aim 2 tests whether inflammation increases frequency of mouse prostatic Srd5a2+ fibroblasts and
whether depletion of these fibroblasts resolves inflammation-mediated collagen accumulation and voiding
dysfunction. Aim 3 will test whether CTGF overexpression is sufficient to drive mouse prostatic collagen
accumulation and voiding dysfunction and whether an investigational new CTGF blocking drug resolves the
problems. The proposed studies will pinpoint CTGF expression in SRD5A2+ fibroblasts as a therapeutic target
for treating lower urinary tract symptoms. By establishing mechanistic connections between inflammation, CTGF
and COL1A2 abundance, and urinary dysfunction, the studies launch an original line of research into a disease
process that is yet-to-be leveraged as a target for medical therapies addressing ...

## Key facts

- **NIH application ID:** 10022318
- **Project number:** 5U54DK104310-07
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Douglas William Strand
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $141,743
- **Award type:** 5
- **Project period:** 2014-09-24 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022318

## Citation

> US National Institutes of Health, RePORTER application 10022318, CTGF drives voiding dysfunction through expression of collagen in periurethral SRD5A2+ fibroblasts (5U54DK104310-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10022318. Licensed CC0.

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