# Role of lung endothelial cells during fibrotic lung remodeling.

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $550,773

## Abstract

Summary
Chronic epithelial or vascular injuries followed by dysregulated repair are the trigger mechanisms in
pathogenesis of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF). Multiple cell types are
involved in lung fibrogenesis, with fibroblasts and epithelial cells given the most attention. Role of endothelial
cells and microvasculature remain unclear. Dysregulated repair causes vascular remodeling, associated with
increased vessel permeability, partial loss of capillaries, focal increase in pathological angiogenesis and
endothelial dysfunction. Normal endothelial cells (EC) are transcriptionally re-programmed into fibrosis-
associated endothelial cells (FEC), that support activated fibroblasts and promote lung inflammation. Our long-
term goal is to identify key regulators of EC-to-FEC re-programming and clarify molecular mechanisms of the
crosstalk between endothelial cells and other cell types during pulmonary fibrogenesis. In our preliminary data,
we used endothelial cells from lungs of patients with IPF and mouse lung fibrosis models to identify FOXF1 as
a key transcriptional regulator of EC-to-FEC re-programming during lung fibrogenesis. Using transgenic mouse
models with endothelial-specific deletion or over-expression of Foxf1 gene, we propose to test the hypothesis
that endothelial FOXF1 decreases activation of fibroblasts and prevents macrophage accumulation in fibrotic
foci. We propose two specific aims: (1) identify molecular mechanisms whereby endothelial FOXF1 inhibits
lung fibrogenesis, (2) establish whether restoring FOXF1 in FECs will prevent or reduce fibrotic lung
remodeling after chronic lung injury. Understanding the regulation of EC-to-TEC re-programming, and the
molecular mechanisms utilized by pulmonary endothelial cells to control pulmonary fibrosis, will provide new
approaches for treatment of interstitial lung diseases.

## Key facts

- **NIH application ID:** 10435583
- **Project number:** 5R01HL158659-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Tanya Kalin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $550,773
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435583

## Citation

> US National Institutes of Health, RePORTER application 10435583, Role of lung endothelial cells during fibrotic lung remodeling. (5R01HL158659-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10435583. Licensed CC0.

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