# Impact of mechanical stretch on the progression of pulmonary fibrosis in mouse bleomycin model

> **NIH NIH R03** · UNIVERSITY OF VIRGINIA · 2024 · $158,419

## Abstract

Project title: Impact of mechanical stretch on the progression of pulmonary fibrosis in bleomycin model of young and old mice
Abstract
Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease. The main histological pattern of IPF is usual interstitial
pneumonia with advanced scarring and microscopic honeycombing, which are predominantly found in immediate subpleural
parenchyma of peripheral and lower lung, but relatively spared in the central and upper lobule. Our recently published study of
IPF lung show that the central lung tissues display massive deregulated gene expressions associated with IPF signaling pathway,
indicating that central region are also subjected to the injuries for IPF initiation. These findings raise a critical question for IPF
development: why only the peripheral and lower lobs undergo continuing progression to massive architecture abnormities and
scar formation, while the central and upper regions remain histologically stable upon activation of IPF signaling pathway.
Intriguingly, radiology report of healthy subject has shown that the degree of lung expansion (DLE) during inspiration and
expiration circle also demonstrates spatial imbalance, with much larger DLE in peripheral and lower lung than in central and
upper lung. The perpetual mechanical stretching associated with the DLE has been reported to exert profound influence in the
repair of lung epithelial cells and remodeling of cancer associated fibroblasts. We hypothesize that the diaphragmatic
breathing-associated mechanical tension may stimulate the progression of pulmonary fibrosis (PF) in the lower lung
with preexisting injury. Accordingly, we propose a novel animal model to investigate the impact of unilateral diaphragmatic
paralysis (UDP) on PF progression after bleomycin induction, in order to unveil the hidden intrinsic mechanisms underpinning
PF progression.
Mechanotransduction is the process by which cells convert mechanical signals, such as physical forces or movements, into
biochemical signals that can affect cell behavior. This process is important for many cellular functions, including tissue
development and remodeling after injury. Our previous studies indicate thatThy-1 mediates mechanotransduction by interacting
with integrins to conciliate cellular responses to mechanical cues. Aging is associated with increased susceptibility of IPF. Thy-1
expression in the lung decreases with age. Loss of Thy-1 expression on lung cells led to increased fibrosis in response to lung
injury. Other studies have suggested that targeting Thy-1 may be a potential strategy for treating lung fibrosis. Therefore, we will
compare the impact of mechanical stretch on PF model in young and old mice.
IPF is a progressive disease, which can further reduce patient's life quality over time. Our proposal will lead to a novel PF model
that can better elucidate the spatial disparity of pathological progression in IPF patients. We will evaluate whether the reduced
mechanical s...

## Key facts

- **NIH application ID:** 10791480
- **Project number:** 1R03AG085239-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Yong Huang
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $158,419
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10791480

## Citation

> US National Institutes of Health, RePORTER application 10791480, Impact of mechanical stretch on the progression of pulmonary fibrosis in mouse bleomycin model (1R03AG085239-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10791480. Licensed CC0.

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