Telocyte-derived exosomes promote angiogenesis and alleviate acute respiratory distress syndrome via JAK/STAT-miR-221-E2F2 axis.

Summary

Exosomes from LPS-stimulated telocytes enhanced angiogenesis and endothelial migration/proliferation via miR-221 targeting E2F2, under JAK/STAT regulation. In an LPS-induced ARDS mouse model, telocyte exosomes reduced lung inflammation and tissue injury; these benefits were abrogated by miR-221 inhibition.

Key Findings

• Telocyte-derived exosomes promoted tube formation, migration, and proliferation in mouse vascular endothelial cells.
• miR-221 mediated pro-angiogenic effects by directly targeting E2F2 (validated by dual-luciferase assay).
• JAK/STAT signaling regulated miR-221 expression; pathway inhibition reduced miR-221 and angiogenic responses.
• In LPS-induced ARDS mice, exosomes reduced lung inflammation and tissue injury; effects were reversed by miR-221 inhibition.

Clinical Implications

Although preclinical, exosome-based strategies targeting the miR-221–E2F2 axis could offer adjunctive therapy for ARDS. Translation will require safety, dosing, biodistribution studies and standardized GMP-grade exosome production.

Limitations

• LPS-induced murine ARDS model may not fully recapitulate human ARDS heterogeneity.
• Exosomes derived from mouse telocytes; lack of large-animal validation, safety, and dose–response data.

Future Directions

Test human telocyte/exosome preparations, define dosing and biodistribution, compare exosome sources, and evaluate efficacy in large-animal and clinically relevant ARDS models.