Intranasal Fritillaria taipaiensis nanovesicles alleviate acute lung injury via the lung-brain axis
Rao, H.; Pan, J.; Guo, J.; Song, X.; Gong, S.; Zhou, T.; Wu, Q.; Huang, Y.; Nie, W.; Peng, C.; Li, Z.; Ren, C.; Pei, J.
Show abstract
Acute lung injury (ALI) is a severe inflammatory syndrome frequently complicated by brain injury, which worsens outcomes. Here, we explored whether regulation of the lung-brain axis represents a therapeutic strategy for the management of ALI. We show that intranasal administration of Fritillaria taipaiensis-derived exosome-like nanovesicles (Ft-ELNs) ameliorates LPS-induced ALI and ALI-associated hypothalamic inflammation in mice. Ft-ELNs preferentially accumulate in the lungs, inhibiting TRPV1 in both the lungs and the hypothalamus to establish the lung-brain axis. In parallel, Ft-ELNs primarily regulate systemic humoral immunity by inhibiting the VEGFR1/PI3K/AKT/NF?B signaling pathway. In vitro experiments further confirmed that Ft-ELNs are efficiently internalized by alveolar epithelial MLE-12 cells, exerting protective effects by suppressing VEGFR1 expression. Mechanistically, we identified Ft-miR1 of Ft-ELNs as the key functional effector that directly targets the Flt1 3'UTR to inhibit VEGFR1 expression. These data suggest that Ft-ELNs attenuate lung-brain axis inflammation by targeting VEGFR1 and may hold potential as novel therapeutic agents for the treatment of severe ALI.
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