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Alveolar Epithelial Cell Dysfunction in Acute Respiratory Distress Syndrome: Mechanistic Insights and Targeted
1Department of Physiology, School of Medicine, Southeast University, Nanjing 210009, China.
Biomedicines
|September 27, 2025
Summary
Alveolar epithelial cell (AEC) dysfunction drives acute respiratory distress syndrome (ARDS). This review explores AEC injury mechanisms and emerging targeted therapies, including gene-based approaches and microbiome modulation, for improved ARDS treatment.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Regenerative Medicine
Background:
- Acute respiratory distress syndrome (ARDS) is a critical illness with significant mortality.
- Alveolar epithelial cell (AEC) dysfunction is a key factor in ARDS pathogenesis, causing barrier disruption and inflammation.
Purpose of the Study:
- To review mechanisms of AEC injury in ARDS.
- To evaluate emerging AEC-targeted therapies and complementary strategies for ARDS treatment.
Main Methods:
- Comprehensive review of literature on ARDS pathogenesis and AEC injury.
- Analysis of single-cell sequencing and spatial transcriptomics data.
- Evaluation of pharmacologic, biologic, and gene-based therapeutic approaches.
Main Results:
- Key AEC injury mechanisms include programmed cell death, oxidative stress, mitochondrial dysfunction, epigenetic changes, and metabolic rewiring.
- Multicellular crosstalk and the gut-lung axis significantly influence ARDS progression.
- Emerging therapies target AECs directly or modulate the microbiome and immune responses.
Conclusions:
- Understanding AEC dysfunction mechanisms is crucial for developing effective ARDS therapies.
- Precision medicine, microbiome modulation, and regenerative approaches offer promising avenues for ARDS treatment.
- Overcoming translational hurdles is essential for advancing epithelium-centered therapies for ARDS.
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