# Luminal epithelial junctions, polarity, and permeability in BPH pathogenesis

> **NIH NIH U54** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $218,675

## Abstract

Project Summary
Benign prostatic hyperplasia (BPH) is one of the most common disease conditions in older men. Although
BPH is not life threatening, its symptoms significantly impact quality of life and treatment costs over $4 billion
annually. Prostatic inflammation is a major factor associated with BPH, which can result in stromal fibrosis and
can reduce the integrity of the epithelial barrier by altering cellular junctions. In preliminary studies, we
identified the presence of luminal epithelial secretory protein, PSA, in the stromal compartment of BPH
nodules. Additionally, we found that adherens junction protein E-cadherin was down-regulated in BPH tissues
as well as in a rat model of prostate inflammation. These findings led to our hypothesis that prostate
inflammation causes disruption of epithelial cell-cell junctions and/or loss of polarity via E-cadherin
down-regulation and subsequently leakage of prostatic secretions such as PSA into the prostatic
stroma compartment. We propose to determine the mechanism of PSA leakage into the BPH stroma via
accomplishing the following Specific Aims: 1) To determine if cellular junctions in prostatic luminal epithelial
cells are altered and associated with PSA leakage into the stromal compartment in BPH specimens; 2) To
determine the role of inflammation in increased prostatic epithelial permeability; 3) To determine the effect of
E-cadherin knockout/knockdown on cellular junctions and leakage of the prostate epithelial layer. The success
of the above specific aims will define changes of luminal epithelial permeability in BPH, lay down a foundation
to further explore mechanisms leading to leakage of epithelial secretions into BPH stroma compartment, and
uncover the contribution of the epithelial secretion leaked into the stromal compartment to BPH pathogenesis.
Defining the mechanisms leading to and consequences of prostatic epithelial leakage may lead to new targets
for prevention and/or treatment of BPH/LUTS.

## Key facts

- **NIH application ID:** 10002344
- **Project number:** 5U54DK112079-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Zhou Wang
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,675
- **Award type:** 5
- **Project period:** 2016-09-22 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002344

## Citation

> US National Institutes of Health, RePORTER application 10002344, Luminal epithelial junctions, polarity, and permeability in BPH pathogenesis (5U54DK112079-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10002344. Licensed CC0.

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