Circulating miR-378a-3p attenuates pulmonary inflammation and fibrosis via BAT-lung crosstalk - PubMed
5 hours ago
- #miR-378a-3p
- #Brown Adipose Tissue
- #Pulmonary Fibrosis
- The study identifies brown adipose tissue (BAT) as a major source of circulating exosomal miR-378a-3p, which reduces pulmonary fibrosis (PF).
- Activation of BAT through cold exposure or β3-adrenergic stimulation increases circulating and lung miR-378a-3p, attenuating collagen buildup and inflammation.
- Deletion of miR-378a-3p in adipocytes worsens lung inflammation and fibrosis, while its overexpression or intravenous delivery of BAT-derived exosomes improves PF symptoms.
- Inhibition of exosome release from BAT reduces circulating miR-378a-3p and blunts the anti-fibrotic effects, supporting a BAT-to-lung communication mechanism.
- Mechanistically, miR-378a-3p targets Itga5 to suppress fibroblast activation via FAK-PI3K-AKT signaling and targets Fstl1 to reduce macrophage inflammation via NF-κB inhibition.
- The findings highlight miR-378a-3p as a BAT-derived molecule with dual anti-inflammatory and anti-fibrotic roles, expanding BAT's role in inter-organ communication in lung diseases.