# Pulmonary Fibrosis Regulation by miR-1

> **NIH NIH U54** · JACKSON STATE UNIVERSITY · 2020 · $171,806

## Abstract

Summary/Abstract: 
 Fibrotic diseases are associated with high morbidity and mortality. Pulmonary fibrosis (PF) is a progressive 
disease with no effective treatment except lung transplant. PH is also a risk factor for other health 
complications including lung cancer. A major characteristic of PF is increased deposition of extracellular matrix 
(ECM) that leads to lung tissue stiffening and loss of function. PF is a heterogeneous disease characterized by 
aberrant signaling pathways of oxidative stress (OS), TGFβ, and NF-κB. We have previously reported 
increased ROS and activation of MAPK, NF-κB, and TGFβ in alveolar epithelial cells following treatment with 
known lung fibrotic toxicants silica and multi-walled carbon nanoparticles (MWCNT). Our previous studies also 
showed increased expression of Col3A1 and TGFβ in alveolar epithelial cells in response to MWCNT. While 
PF is multifactorial, studies have linked reactive oxygen species (ROS) and aberrant microRNAs (miRs) in lung 
fibrosis development. How exactly ROS regulate miRs that drive lung fibrosis development remains largely 
unknown and is the focus of the present application. In our study of human alveolar epithelial (A549) cells 
exposed to MWCNT, we found that: (1) miR-1 is downregulated; (2) TSP-1 is up-regulated; and (3) exogenous 
mimic miR-1 suppresses TSP-1, a major activator of TGFβ. These findings suggest that miR-1 and TSP-1 are 
regulated by MWCNT and targeting miR-1 and TSP-1 might inhibit TGFβ-mediated fibrotic response. The 
central hypothesis of the current project is that ROS suppress miR-1 which promotes increased TSP-1 and 
active TGFβ fibrotic signaling. Specific aims are: (1) determine the mechansims by which miR-1 is regulated; 
(2) determine the mechanistic link between miR-1 and fibrotic signaling via TSP-1/TGFβ (or other pathways 
emerging from mRNASeq data); and (3) determine the function of miR-1 in lung fibrosis in vivo by analyzing 
whether a model of bleomycin- and MWCNT-lung fibrosis in mice and exogenous miR-1 treated mice are less 
prone to lung fibrosis than control miR-1 untreated mice. The proposed study will elucidate cellular and 
molecular mechanism involved in lung fibrosis by targeting TSP-1 via miR-1. This hypothesis, if proven, will 
establish a potential microRNA therapy in pulmonary fibrosis.

## Key facts

- **NIH application ID:** 10145507
- **Project number:** 1U54MD015929-01
- **Recipient organization:** JACKSON STATE UNIVERSITY
- **Principal Investigator:** Maricica Pacurari
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $171,806
- **Award type:** 1
- **Project period:** 2020-09-08 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145507

## Citation

> US National Institutes of Health, RePORTER application 10145507, Pulmonary Fibrosis Regulation by miR-1 (1U54MD015929-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10145507. Licensed CC0.

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