# Impact of alcohol on lung fibroblast regulation of the alveolar epithelial barrier

> **NIH NIH R03** · EMORY UNIVERSITY · 2021 · $78,000

## Abstract

Project Summary
 Tissue disrepair following injury leads to organ dysfunction and increases morbidity and mortality of
those who survive the initial insult. In the lung, the disrepair process is associated with excessive collagen
deposition along with failure of both re-epithelialization and epithelial cell tight junction formation. Tissue
disrepair is associated with dysregulation of TGFβ signaling in a variety of pulmonary diseases including the
acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and interstitial
lung disease (ILD). Our laboratory utilizes experimental models of chronic alcohol ingestion and bleomycin-
induced lung injury to assess the molecular mechanisms of lung repair and identify novel preventative and
therapeutic interventions. We have previously shown that alcohol induces excessive and persistent TGFβ
expression in the lung. Additionally, we demonstrated that in the lung of chronic alcohol-exposed animals,
TGFβ is a critical molecule driving many cellular anomalies by increasing airway oxidative stress, decreasing
alveolar macrophages phagocytosis, and priming the lung for fibroproliferative disrepair following acute injury.
Our preliminary data show that alcohol-exposed lung fibroblasts interfere with epithelial cell barrier formation
likely through induction of epithelial-mesenchymal transition (EMT). Additionally, inhibition of TGFβ signaling
attenuates the effect of alcohol-exposed fibroblasts on epithelial cells. Interestingly, we also showed that
fibroblasts influence epithelial cells indirectly via fibroblast-derived exosomes rather than direct secretion of
cytokines or growth factors. Furthermore, we showed that alcohol disturbs the balance of pro- and anti-fibrotic
microRNA (miR) expression. Specifically, alcohol increases pro-fibrotic miR-21 and attenuates anti-fibrotic
miRNA-1946a in lung fibroblasts. These data lead us to hypothesize that alcohol exposure disrupts alveolar
epithelial cell tight junction formation and barrier function following injury through an imbalance of miR-21 and
miR-1946a in exosomes secreted by lung fibroblasts. The experimental approaches are designed to test this
hypothesis, and these studies are expected to provide a firm scientific basis for the underlying mechanism(s)
by which alcohol interferes with normal repair following lung injury. The results from this proposal will set the
basis for future studies to investigate potential therapeutic strategies to prevent or mitigate tissue injury and
disrepair in the at-risk population (i.e., alcoholic individuals).

## Key facts

- **NIH application ID:** 10263149
- **Project number:** 5R03AA027662-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** VIRANUJ SUEBLINVONG
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $78,000
- **Award type:** 5
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263149

## Citation

> US National Institutes of Health, RePORTER application 10263149, Impact of alcohol on lung fibroblast regulation of the alveolar epithelial barrier (5R03AA027662-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10263149. Licensed CC0.

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