# Impact of Inflammation on Adult Prostate Stem Cells

> **NIH NIH R01** · PURDUE UNIVERSITY · 2020 · $620,771

## Abstract

Benign prostatic hyperplasia (BPH) is defined by the expansion of both epithelial and stromal cells within the
transition zone of the prostate. Although there is greater expansion of stromal cells in early BPH, epithelial
hyperplasia is a significant contributor to larger symptomatic BPH prostates. While numerous studies have linked
chronic and recalcitrant inflammation to the development of BPH, the mechanisms by which inflammation leads
to cellular proliferation and hyperplasia are unclear. It is known that inflammation produces a microenvironment
rich in cytokines, growth factors, and other morphogens that promote proliferation of prostate epithelial cells,
including basal prostate stem cells (bPSC). The regulatory mechanisms that control and limit inflammation-
induced epithelial cell proliferation under normal homeostatic conditions are not well defined and represent a
significant deficit in understanding the potential link between inflammation, uncontrolled cellular growth and
prostate enlargement. Data reported herein identify pathways controlling prostate epithelial cell expansion and
form the foundation for proposed studies to better define the regulation of inflammation-induced prostate
epithelial cell proliferation that leads to hyperplasia. Understanding the pathways involved in inflammation-
induced cellular expansion will provide a foundation for the development of novel approaches to block
uncontrolled epithelial growth.
 Adult basal prostate stem cells (bPSC) are specialized cells that maintain and repair the cellular integrity of
the prostate; however, studies describing the effect of inflammation on adult bPSC are limited. Previous data
from our laboratories show that inflammation stimulates bPSC expansion and generates basal and luminal
epithelial hyperplasia in vivo as well as larger organoids compared to non-inflamed (naïve) bPSC ex vivo,
demonstrating a sustained proliferative effect on these cells. Given that inflammation drives a bPSC to luminal
cell transition, which requires androgen receptor (AR) and the data reported herein that inflammation stabilizes
AR via phosphorylation and IL-1α and its naturally occurring inhibitor, IL-1ra, where IL-1α inhibits AR expression
and IL1ra enhances expression leading to bPSC-driven expansion of epithelial cells. Based on these data, we
hypothesize that inflammation drives AR stabilization that drives bPSC expansion and epithelial
hyperplasia in BPH. To test the hypothesis we propose to define the molecular basis for inflammation induced
AR stabilization, evaluate pathway impact using novel genetically modified mice and define AR-dependent
programmatic changes in bPSC linked both to proliferation and epithelial hyperplasia.

## Key facts

- **NIH application ID:** 10072966
- **Project number:** 1R01DK126478-01
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Timothy L. Ratliff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $620,771
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072966

## Citation

> US National Institutes of Health, RePORTER application 10072966, Impact of Inflammation on Adult Prostate Stem Cells (1R01DK126478-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072966. Licensed CC0.

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