Jujuboside A-Loaded Exosomes Alleviate Pulmonary Fibrosis via TGF-β/Smad and Autophagy Regulation

This study aimed to scrutinize the antifibrotic effects of jujuboside A-loaded exosomes (JuA-Exo) on TGF-β1-induced MRC-5 fibroblasts and explore the pathophysiological basis. Exosomes were isolated from human mesenchymal stem cells and loaded with JuA by ultrasonic dispersion. A TGF-β1-induced MRC-5 fibrosis model was established. Cell viability, migration capacity, levels of inflammatory cytokines, extracellular matrix components, and autophagy-related markers were assessed. To determine autophagy dependence, the autophagy inhibitor 3-methyladenine (3-MA) was employed. JuA-Exo significantly attenuated fibroblast activation triggered by TGF-β1, decreased the secretion of IL-6, IL-1β, and hydroxyproline, and downregulated fibrotic gene expression, including α-SMA, fibronectin, COL1A1, and COL3A1. Mechanistically, JuA-Exo was associated with modulation of the TGF-β/Smad signaling pathway and restoration of autophagy-related markers. Importantly, the defensive effects of JuA-Exo were reversed upon autophagy inhibition by 3-MA. JuA-Exo exerts antifibrotic and anti-inflammatory effects, which are associated with modulation of TGF-β/Smad signaling and autophagy-related processes; however, the mechanistic linkage between these pathways and their causal roles requires further validation. These findings highlight JuA-Exo as a potential experimental candidate, although the current evidence is limited to in vitro observations and does not yet support therapeutic application.Impact StatementThis study demonstrates that jujuboside A-loaded exosomes exert antifibrotic and anti-inflammatory effects in vitro, providing mechanistic insight and highlighting a potential nanotherapeutic approach that warrants further validation.