Related Experiment Video
Updated: Mar 13, 2026
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
The role of microRNA-155/liver X receptor pathway in experimental and idiopathic pulmonary fibrosis
Mariola Kurowska-Stolarska1, Manhl K Hasoo1, David J Welsh2
1Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
Background:
Idiopathic pulmonary fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF; therefore, microRNAs may reveal novel pathogenic pathways.
Objectives:
We sought to determine the regulatory role of microRNA (miR)-155 in the profibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts, and its contribution to experimental pulmonary fibrosis.
Methods:
Bleomycin-induced lung fibrosis in wild-type and miR-155-/- mice was analyzed by histology, collagen, and profibrotic gene expression. Mechanisms were identified by in silico and molecular approaches and validated in mouse lung fibroblasts and macrophages, and in IPF lung fibroblasts, using loss-and-gain of function assays, and in vivo using specific inhibitors.
Results:
miR-155-/- mice developed exacerbated lung fibrosis, increased collagen deposition, collagen 1 and 3 mRNA expression, TGF-β production, and activation of alternatively activated macrophages, contributed by deregulation of the miR-155 target gene the liver X receptor (LXR)α in lung fibroblasts and macrophages. Inhibition of LXRα in experimental lung fibrosis and in IPF lung fibroblasts reduced the exacerbated fibrotic response. Similarly, enforced expression of miR-155 reduced the profibrotic phenotype of IPF and miR-155-/- fibroblasts.
Conclusions:
We describe herein a molecular pathway comprising miR-155 and its epigenetic LXRα target that when deregulated enables pathogenic pulmonary fibrosis. Manipulation of the miR-155/LXR pathway may have therapeutic potential for IPF.
Insights
MicroRNA-155 plays a protective role in pulmonary fibrosis by regulating the liver X receptor alpha (LXRα). Targeting the miR-155/LXRα pathway may offer new therapeutic strategies for idiopathic pulmonary fibrosis (IPF).
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Epigenetics
Background:
- Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with poorly understood pathogenesis.
- Epigenetic modifications, including microRNAs (miRNAs), are implicated in IPF development.
- MicroRNAs offer potential as biomarkers and therapeutic targets in IPF.
Purpose of the Study:
- To investigate the role of microRNA (miR)-155 in the profibrotic functions of lung cells.
- To determine miR-155's contribution to experimental pulmonary fibrosis.
- To elucidate the molecular mechanisms underlying miR-155's function in fibrosis.
Main Methods:
- Analysis of bleomycin-induced lung fibrosis in wild-type and miR-155 knockout mice.
- Histological, collagen, and gene expression analyses.
- In silico and molecular approaches to identify miR-155 targets, validated in vitro and in vivo.
Main Results:
- miR-155 deficiency exacerbated lung fibrosis, collagen deposition, and TGF-β production.
- Dysregulation of the miR-155 target gene liver X receptor alpha (LXRα) was observed.
- Inhibition of LXRα and enforced miR-155 expression modulated fibrotic responses in experimental models and IPF cells.
Conclusions:
- A molecular pathway involving miR-155 and its target LXRα is crucial in pulmonary fibrosis pathogenesis.
- Deregulation of the miR-155/LXRα axis contributes to IPF.
- Modulating the miR-155/LXRα pathway presents a potential therapeutic strategy for IPF.
More Related Videos
06:29Adoptive Transfer of IL-33-Stimulated Macrophages into Bleomycin-Induced Mouse Models to Study Their Effect on Idiopathic Pulmonary Fibrosis In Vivo
Published on: May 5, 2023
03:38Unilateral Lung Volume Analysis Using Micro-CT for Enhanced Assessment of Pulmonary Fibrosis in Preclinical Models
Published on: June 20, 2025
