Acute lung injury (ALI) is characterized by protein-rich pulmonary edema, critical
hypoxemia, and influx of pro-inflammatory cytokines and cells. There are currently
no effective pharmacon therapies in clinical practice. Syndecan-1 in endothelial cells
has potential to protect barrier function of endothelium and suppress inflammation
response. Thus, the present study was to identify whether exosomes with encapsulation
of syndecan-1 could achieve ideal therapeutic effects in ALI. Exosomes were isolated
from the conditional medium of lentivirus-transfected mouse pulmonary microvascular
endothelial cells (MPMVECs) and characterized by nanoparticle tracking analysis (NTA),
transmission electron microscopy (TEM), and western blotting. ALI mouse models were
induced via intratracheal administration of lipopolysaccharide (LPS) and treated with
exosomes. Lung edema, inflammation, and glycocalyx thickness were examined. The possible
mechanism was verified by immunoblotting in MPMVECs. The purified exosomes included
SDC1-high-Exos and SDC1-low-Exos which loaded with up-regulated syndecan-1 and down-regulated
syndecan-1 respectively. Compared with SDC1-low-Exos, administration of SDC1-high-Exos
could ameliorate lung edema and inflammation, attenuate number of cells and protein
levels in bronchoalveolar lavage fluid (BALF), and preserve glycocalyx. Furthermore,
SDC1-high-Exos also mitigated the expression of pro-inflammatory cytokines such as
IL-1β, TNF-α, and IL-6 following LPS challenge. In MPMVECs, SDC1-high-Exos decreased
stress fiber formation and ameliorated monolayer hyper-permeability after LPS stimulation.
Western blotting analysis demonstrated that FAK/p190RhoGAP/RhoA/ROCK/NF-κB signaling
pathway may be involved in LPS-induced ALI. In conclusion, SDC1-high-Exos play a pivotal
role in ameliorating LPS-stimulated ALI models and may be served as a potential therapeutic
agent for clinical application in the future.