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Updated: Sep 26, 2025
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
MiR-130a-3p Alleviates Inflammatory and Fibrotic Phases of Pulmonary Fibrosis Through Proinflammatory Factor TNF-α
Yan Ding1, Yapeng Hou1, Yanhong Liu1
1Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, China.
Abstract:
Pulmonary fibrosis (PF) is a progressive disease characterized by extracellular matrix (ECM) deposition that destroys the normal structure of the lung parenchyma, which is classified into two successive inflammatory and fibrotic phases. To investigate the anti-inflammatory and anti-fibrotic roles of miR-130a-3p in mice with bleomycin (BLM)-induced PF and the underlying mechanism, we performed single-cell RNA-sequencing analysis, which demonstrated that BLM increased/decreased the percentage of macrophages and fibroblasts/epithelial cells in PF lungs, respectively. The differentially expressed genes were enriched in PPAR signaling pathway and lysosome, ECM-receptor interaction and ribosome, and metabolism reaction. Time-course studies demonstrated that the inflammation-related factors increased significantly at day 7 (inflammatory phase), whereas the fibrosis-related factors increased at day 28 (fibrotic phase) after BLM exposure. Meanwhile, miR-130a-3p could ameliorate pulmonary lesions by downregulating the secretion of inflammatory cytokines (IL-1β, IL-6, TNF-α, and TGF-β1) and the deposition of ECM (α-SMA, FN, HYP, and collagen) in the inflammatory and fibrotic phase, respectively. In the LPS-induced inflammatory cell model, the upregulation of miR-130a-3p was mainly achieved by the activation of the NF-κB signaling pathway, which suppressed the proinflammatory factor TNF-α. Comparatively, the TGF-β/Smad signaling pathway was inhibited by miR-130a-3p targeting TGF-βRII in the TGF-β1-deduced fibrotic cell model. The evidence supports that miR-130a-3p exerts an anti-inflammatory and anti-fibrotic effect in BLM-induced PF, implying a potential pharmacological agent in the therapy of PF patients.
Insights
MicroRNA-130a-3p shows promise for treating pulmonary fibrosis (PF). This study found it reduces inflammation and fibrosis in mice by targeting key signaling pathways, suggesting its potential as a therapeutic agent.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Immunology
Background:
- Pulmonary fibrosis (PF) is a progressive lung disease marked by extracellular matrix deposition, involving distinct inflammatory and fibrotic phases.
- Bleomycin (BLM)-induced PF in mice serves as a model to study disease progression and potential therapeutic interventions.
Purpose of the Study:
- To investigate the anti-inflammatory and anti-fibrotic roles of microRNA-130a-3p (miR-130a-3p) in a mouse model of BLM-induced PF.
- To elucidate the underlying molecular mechanisms by which miR-130a-3p modulates inflammatory and fibrotic processes.
Main Methods:
- Single-cell RNA sequencing was employed to analyze cellular composition changes in PF lungs.
- Time-course studies assessed the dynamics of inflammation and fibrosis markers post-BLM exposure.
- In vitro cell models (LPS-induced and TGF-β1-induced) were used to examine miR-130a-3p's effects on specific signaling pathways (NF-κB and TGF-β/Smad).
Main Results:
- BLM induced significant alterations in lung cell populations, increasing macrophages and decreasing epithelial cells.
- miR-130a-3p ameliorated pulmonary lesions by downregulating inflammatory cytokines (e.g., IL-1β, TNF-α, TGF-β1) and extracellular matrix components (e.g., α-SMA, collagen).
- miR-130a-3p suppressed inflammation via the NF-κB pathway and inhibited fibrosis by targeting TGF-βRII within the TGF-β/Smad pathway.
Conclusions:
- miR-130a-3p demonstrates significant anti-inflammatory and anti-fibrotic effects in BLM-induced pulmonary fibrosis.
- The findings support miR-130a-3p as a potential therapeutic agent for pulmonary fibrosis patients.
