# The role of microRNA-1946a in fibroproliferative disrepair following an acute lung injury

> **NIH NIH R03** · EMORY UNIVERSITY · 2020 · $78,000

## Abstract

Project Summary
 In the United States (U.S.), the acute respiratory distress syndrome (ARDS) remains a significant public
health problem. Despite substantial efforts to improve the outcome, mortality remains ~45%. More importantly,
~ 80% of ARDS survivors experience reduced health-related quality of life, and these survivors also have
changes consistent with early fibrosis on chest imaging for up to 5 years after a diagnosis of ARDS. Although
there is no direct evidence that fibroproliferative ARDS is associated with an increase in mortality, indirect
evidence suggests an increased risk of death in patients with elevated pro-fibrotic markers, transforming
growth factor-beta (TGFβ) and procollagen III in the bronchoalveolar lavage. Dysregulation of TGFβ drives
tissue disrepair following injury. Our laboratory utilizes experimental models of chronic alcohol ingestion and
bleomycin-induced acute lung injury (ALI) to assess the molecular mechanisms of lung repair as well as
identify novel preventative and therapeutic interventions. We showed that alcohol induced excessive and
persistent TGFβ expression in the lung. We showed that TGFβ is a key molecule that drives many cellular
anomalies in the lung of chronic alcohol-exposed animals including increase oxidative stress in the airway,
decrease in alveolar macrophages phagocytosis, and primes the lung toward fibroproliferative disrepair
following acute injury. Elucidating the mechanisms by which TGFβ being induced in the lung would allow the
development of novel strategies to promote effective repair following ALI. Our preliminary data show that one
of the mechanism by which alcohol induces TGFβ is by disturbing 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. Very little is known regarding the function of miR-1946a and how it is
regulated. In silico analysis showed that miR-1946a targeted TGFβ, in this proposal, we show that inhibition of
miR-1946a increases TGFβ expression while overexpression of miR-1946a attenuates TGFβ expression. This
is the first direct evidence suggesting the role of miR-1946a on TGFβ expression. These exciting results lead
us to hypothesize that alcohol increases TGFβ expression by inhibiting anti-fibrotic miR-1946a, thereby priming
the lung for fibroproliferative disrepair. The experimental approaches are designed to test this hypothesis, and
these studies are expected to provide a firm scientific basis for the underlying mechanisms by which alcohol
interferes with normal repair following ALI.

## Key facts

- **NIH application ID:** 9852929
- **Project number:** 5R03AA027335-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** VIRANUJ SUEBLINVONG
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,000
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852929

## Citation

> US National Institutes of Health, RePORTER application 9852929, The role of microRNA-1946a in fibroproliferative disrepair following an acute lung injury (5R03AA027335-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852929. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*