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Updated: Jul 31, 2025
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
PM2.5 promotes pulmonary fibrosis by mitochondrial dysfunction
En-Ming Chang1, Chia-Chia Chao2, Mei-Ting Wang3
1Department of Respiratory Care, Shin Kong Wu Ho Su Memorial Hospital, Taipei City, Taiwan.
Abstract:
Pulmonary fibrosis is known as an incurable lung disorder with irreversible progression of chronic injury, myofibroblast proliferation, extracellular matrix (ECM) accumulation, and tissue scarring. Atmospheric particulate matter 2.5 (PM2.5 ) is implicated as a risk factor of several diseases, especially lung diseases such as pulmonary fibrosis. The molecular mechanism which participates PM2.5 -induced pulmonary fibrosis in type II alveolar cells (AEII) has yet to be determined. Our results proved that short- and long-term exposure to PM2.5 significantly stimulated epithelial-mesenchymal transition (EMT) activity in AEII cells, according to, changes in gene signature analyzed by RNA-seq and cell morphology. Furthermore, Gene Ontology (GO) enrichment analysis also suggested that mitochondrial dysfunction was related to progression of pulmonary fibrosis in AEII after PM2.5 exposure. We observed a marked decline in mitochondria membrane potential (MMP), as well as fragmented mitochondria, in AEII cells exposed to PM2.5 , which suggests that energy metabolism is suppressed after PM2.5 exposure. We also confirmed that PM2.5 exposure could influence the expression levels of Mfn1, Mfn2, and Drp1 in AEII. Pretreatment of mitochondrial fusion promoter M1 was able to reverse mitochondrial dysfunction as well as EMT in AEII. These data suggested the key role of mitochondrial fragmentation in AEII, which was induced by PM2.5 exposure, and participated pathogenesis of pulmonary fibrosis. Finally, we investigated the response of lung tissue exposed to PM2.5 in vivo. The data indicated that the lung tissue exposed to PM2.5 obviously induced collagen accumulation. Moreover, IHC results revealed that PM2.5 enhanced Drp1 expression but suppressed Mfn1 and Mfn2 expression in lung tissue. The current study provides novel insight of pulmonary fibrosis caused by PM2.5 exposure.
Insights
Particulate matter 2.5 (PM2.5) exposure triggers mitochondrial fragmentation and epithelial-mesenchymal transition (EMT) in lung cells, driving pulmonary fibrosis. Promoting mitochondrial fusion reversed these harmful effects, suggesting a therapeutic target for PM2.5-induced lung disease.
Area of Science:
- Environmental Health
- Cell Biology
- Pulmonary Medicine
Background:
- Pulmonary fibrosis is an irreversible lung disease characterized by scarring.
- Atmospheric particulate matter 2.5 (PM2.5) is a known risk factor for lung diseases, including pulmonary fibrosis.
- The precise molecular mechanisms of PM2.5-induced pulmonary fibrosis in alveolar cells remain unclear.
Purpose of the Study:
- To investigate the molecular mechanisms underlying PM2.5-induced pulmonary fibrosis in type II alveolar epithelial (AEII) cells.
- To explore the role of mitochondrial dysfunction and epithelial-mesenchymal transition (EMT) in this process.
- To evaluate the potential of targeting mitochondrial dynamics for therapeutic intervention.
Main Methods:
- Exposure of AEII cells and mouse lung tissue to PM2.5.
- RNA sequencing (RNA-seq) for gene expression analysis.
- Assessment of cell morphology, mitochondrial membrane potential (MMP), and mitochondrial dynamics (Mfn1, Mfn2, Drp1 expression).
- In vivo studies using immunohistochemistry (IHC) to analyze lung tissue collagen accumulation and protein expression.
Main Results:
- PM2.5 exposure stimulated EMT and mitochondrial dysfunction in AEII cells, evidenced by altered gene expression, cell morphology changes, decreased MMP, and mitochondrial fragmentation.
- PM2.5 altered the expression of mitochondrial dynamics proteins (Mfn1, Mfn2, Drp1) in both AEII cells and lung tissue.
- In vivo PM2.5 exposure led to increased collagen accumulation in lung tissue.
- Pretreatment with a mitochondrial fusion promoter (M1) reversed PM2.5-induced mitochondrial dysfunction and EMT in AEII cells.
Conclusions:
- Mitochondrial fragmentation in AEII cells plays a critical role in PM2.5-induced pulmonary fibrosis.
- PM2.5 exposure disrupts mitochondrial dynamics, contributing to lung tissue damage and fibrosis.
- Targeting mitochondrial fusion presents a potential therapeutic strategy for mitigating PM2.5-related pulmonary fibrosis.
