Extracellular vesicle-mediated transcellular mitophagy as a modulatory target for moderate hyperoxia-induced alveolar developmental arrest in bronchopulmonary dysplasia - PubMed
3 hours ago
- #bronchopulmonary dysplasia
- #mitophagy
- #extracellular vesicles
- Hyperoxia exposure contributes to alveolar developmental arrest in bronchopulmonary dysplasia (BPD).
- Fibroblasts transition to a disease-associated phenotype under moderate hyperoxia (60% oxygen).
- Activated fibroblasts enhance communication with type II alveolar epithelial cells (AEC IIs) via extracellular vesicles (EVs).
- EVs from fibroblasts are enriched with mitochondrial components, particularly VDAC1, inhibiting BNIP3-dependent mitophagy in AEC IIs.
- This inhibition leads to autophagic flux blockade and mitochondrial dysfunction in AEC IIs.
- Inhibition of fibroblast-derived EV release or administration of hUC-MSC-derived EVs attenuates hyperoxia-induced AEC II dysfunction and alveolar impairment.
- The study identifies fibroblast-epithelial communication as a key mechanism in BPD, suggesting potential therapeutic targets.