# The Role of Peroxiredoxin 4 in Idiopathic Pulmonary Fibrosis

> **NIH NIH F31** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $15,152

## Abstract

Project Summary
In the US 40,000 people are diagnosed with idiopathic pulmonary fibrosis (IPF) every year. Diagnosis of IPF is
essentially a death sentence since patient survival is only 2-3 years after diagnosis. Recent advances in
understanding IPF have led to the development of two new drugs to treat IPF, nintedanib and pirfenidone,
however neither drug significantly increases life span after diagnosis. Our research has been focused on
understanding the role or oxidative stress in the onset and progression of IPF. Cellular oxidative stress has long
been linked with IPF, however past treatments with antioxidant compounds have proven ineffective. We believe
that these past therapies have failed because there is a lack of understanding of the mechanisms involved in
oxidative stress at a subcellular level. Through our research, we will gain insight into the underlying mechanisms
and signals associated with cellular oxidative stress in the endoplasmic reticulum (ER). The ER is where a clear
majority of proteins are properly folded, and any changes in the redox status of the ER will have a large impact
on the redox state of many proteins. The new knowledge gained will allow for the development of targeted
antioxidant therapies to treat IPF. We hypothesize that by alleviating oxidative stress in lung epithelial cells we
can halt epithelial cell death and thus stop and reverse the progression of IPF. To test our hypothesis, we will
treat lung epithelial cells with a pro-apoptotic signaling protein, Fas ligand (FasL), and measure levels of a key
cellular oxidant, hydrogen peroxide (H2O2), in the ER. We will then assess the effects of modulating the activity
of the most highly expressed ER H2O2 scavenger, peroxiredoxin 4 (Prdx4), on ER redox homeostasis and cell
death. To further verify our findings, we will conduct studies using a mouse model of pulmonary fibrosis where
we can induce the ablation of, Prdx4. Using this model, we will show the effects of decreasing cellular hydrogen
peroxide levels on the development and progression of pulmonary fibrosis. Finally, we will verify that our findings
are relevant to human IPF by conducting a similar set of experiments to access hydrogen peroxide levels and
protein oxidation states in human IPF lung tissue. Upon completion of our research we will have a better grasp
on the role of oxidative stress in the ER, which can be utilized to create more targeted antioxidant therapies for
treatment of IPF.

## Key facts

- **NIH application ID:** 10022135
- **Project number:** 5F31HL144051-02
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Evan Elko
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $15,152
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022135

## Citation

> US National Institutes of Health, RePORTER application 10022135, The Role of Peroxiredoxin 4 in Idiopathic Pulmonary Fibrosis (5F31HL144051-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10022135. Licensed CC0.

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