# Adhesome signaling in lung injury and repair

> **NIH VA I01** · BIRMINGHAM VA MEDICAL CENTER · 2024 · —

## Abstract

PROJECT SUMMARY
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic lung disease. IPF is
characterized by fibroblast and myofibroblast foci and excessive accumulation of
extracellular matrix (ECM) proteins. IPF is prevalent among the Veteran population.
Myofibroblast differentiation is thought as one of the responsible mechanisms for
excessive ECM protein production and accumulation, leading to progressive fibrotic
lesions in lung. It is important to understand the molecular mechanisms that are
responsible for myofibroblast activation in IPF. Tristetraprolin (TTP) is a major regulator of
gene expression and modulates mRNA stability. The preliminary data demonstrate that
TTP function is impaired in IPF. We speculate that impaired TTP function likely results in
a dysregulated regulation system of gene expression, and consequently leads to
pathological conditions. This proposal aims to investigate the role of TTP as a break to
limit fibrotic response and lung fibrosis. It is important to understand the molecular
mechanism leading to increased pro-fibrotic response in IPF. The preliminary data
demonstrate that TTP regulates ECM protein expression and signaling that are important
for myofibroblast differentiation and functions, and gain of TTP decreases ECM protein
expression and signaling, and myofibroblast differentiation in IPF lung fibroblasts. We
hypothesize that impaired TTP fosters a ‘pro-fibrotic ECM niche’, fueling cell-matrix
interaction and signaling that increases myofibroblast differentiation and fibrotic
responses. This proposal aims to define the role of TTP in myofibroblast differentiation
and lung fibrosis, examine the molecular mechanism involved, determine the impact of
impaired TTP function on ECM production and accumulation, and the role of TTP in
fibrogenesis and fibrotic remodeling in vivo. Completion of this project will provide new
insight about the mechanisms responsible for the development of pulmonary fibrosis and
serve the goal to develop more effective therapy for IPF patients.

## Key facts

- **NIH application ID:** 10804057
- **Project number:** 1I01BX006354-01
- **Recipient organization:** BIRMINGHAM VA MEDICAL CENTER
- **Principal Investigator:** QIANG DING
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804057

## Citation

> US National Institutes of Health, RePORTER application 10804057, Adhesome signaling in lung injury and repair (1I01BX006354-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10804057. Licensed CC0.

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