# LTBP2 regulation of fibrotic lung damage

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2022 · $236,250

## Abstract

Title: LTBP2 regulation of fibrotic lung damage
Summary:
 Latent TGFβ Binding Protein 2 (LTBP2) is an extracellular matrix (ECM) protein. Unlike other proteins in the
LTBP family, LTBP2 does not directly bind or regulate TGFβ activity. However, recent studies found that LTBP2
directly binds to FGF2. LTBP2 is highly expressed in the lung during development and during the pathogenesis
of several pulmonary diseases including idiopathic pulmonary fibrosis (IPF). The elevated expression of LTBP2
in the lung and serum of patients diagnosed with IPF may be useful as a biomarker; however, whether it has a
pathogenic role in IPF is not known.
 IPF is a disease that is characterized by cycles of pulmonary damage and repair that leads to the
accumulation of fibrotic tissue in the lung. Over time, this fibrotic tissue reduces lung function and leads to poor
patient prognosis. There are few effective treatments for IPF, as fibrotic damage is cumulative and permanent.
Myofibroblast dysfunction has been identified as a major component of the lung damage observed in IPF.
Fibroblasts and myofibroblasts are the main cells that express LTBP2 in the lungs of IPF patients, but the role
of LTBP2 in pathogenic fibrosis is not known.
 In preliminary studies, we discovered that mice lacking Ltbp2 gene function develop considerably less
pulmonary fibrosis than wild type mice when challenged with bleomycin, a common model for studying lung
fibrosis. LTBP2 deficient lungs displayed lower collagen content, less extensive fibrosis, and less tissue
destruction after exposure to bleomycin, suggesting that LTBP2 may be functionally involved in the pathogenic
fibrotic response to lung injury. In our previous studies, we have shown that activation of FGF2 can decrease
bleomycin-induced pulmonary fibrosis. We thus hypothesize that one function of LTBP2 could be to limit FGF2
bioavailability during the response to bleomycin-induced lung injury, and indirectly, through competition with
other LTBPs for binding to fibrillin 1, enhance pro-fibrotic TGFβ activity.
 In this proposal, we use a combination of mouse genetic models and bleomycin-induced lung injury, primary
cell culture, and single cell RNA sequencing, to test our hypothesis and identify underlying molecular and genetic
mechanisms for LTBP2-extracellular matrix interactions and LTBP2-regulation of growth factor signaling in the
pathogenesis of lung fibrosis in adult mice. The proposed experiments will also elucidate how key cell types
contribute to fibrotic injury and will identify new genes that could be therapeutically targeted to reduce lung
fibrosis in response to injury.

## Key facts

- **NIH application ID:** 10526774
- **Project number:** 1R21AI167415-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** David M Ornitz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2022-06-02 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526774

## Citation

> US National Institutes of Health, RePORTER application 10526774, LTBP2 regulation of fibrotic lung damage (1R21AI167415-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10526774. Licensed CC0.

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