# Targeted Death of Collagen1a1-Expressing Fibroblasts Reduces Silica-Induced Pulmonary Fibrosis

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2024 · $34,395

## Abstract

PROJECT SUMMARY
A key feature of progressive fibrotic diseases of the lungs, including in patients with silicosis, is the excessive
deposition of scar tissue and extracellular matrix (ECM), particularly collagen1a1 (Col1a1). Fibroblasts are
known to be resistant to apoptosis and persist in fibrotic lungs, continuing to lay down matrix, contributing to a
progressive and persistent phenotype in patients. Fibroblasts that participate in this pathogenic process have
most commonly been identified by αSMA staining and termed myofibroblasts. However, recent work by our group
and others has shown that αSMA does not identify all pathogenic fibroblasts in pulmonary fibrosis. This proposal
seeks to address the central hypothesis that elimination of persistent collagen-producing fibroblasts is critical in
halting disease progression. Based on our robust preliminary studies, we propose three specific aims to test this
central hypothesis. Specific Aim 1 will determine the accumulation and localization of Col1a1+ fibroblasts to the
fibrosis associated after silica exposure using a lineage tracing strategy. We hypothesize that Col1a1+ fibroblasts
accumulate and persist in mouse lungs during silica-induced pulmonary fibrosis. In Aims 2 and 3 we ask if the
loss of Col1a1+ fibroblasts prevents fibrosis progression. Specific Aim 2 will test the hypothesis that the
progression of silica-induced pulmonary fibrosis in mice is arrested after the selective and targeted ablation of
Col1a1+ fibroblasts. Specific Aim 3 will test the hypothesis that genetic loss of the anti-apoptotic protein Bcl-2 in
Col1a1+ fibroblasts promotes their susceptibility to undergo intrinsic apoptosis during silica-induced pulmonary
fibrosis resulting in the arrest of disease progression. There are currently no FDA approved therapies for silicosis
and no therapies that stop or reverse fibrosis for pulmonary fibrosis in general. Thus, there is a critical need to
identify molecular pathways or cell populations that are targetable for therapeutic intervention. Additionally, the
proposed studies will provide a novel and mechanistic understanding about pathogenic fibroblast accumulation
and persistence in driving the progression of silica-induced pulmonary fibrosis.

## Key facts

- **NIH application ID:** 10929390
- **Project number:** 5F31HL170750-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Daniel G Foster
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $34,395
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929390

## Citation

> US National Institutes of Health, RePORTER application 10929390, Targeted Death of Collagen1a1-Expressing Fibroblasts Reduces Silica-Induced Pulmonary Fibrosis (5F31HL170750-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10929390. Licensed CC0.

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