Telocyte-derived exosomes promote angiogenesis and alleviate ARDS via JAK/STAT-miR-221-E2F2 axis
Acute respiratory distress syndrome (ARDS) is characterized by severe respiratory failure and significant inflammation, leading to vascular and epithelial cell damage. The absence of effective pharmacologic treatments underscores the need for novel therapeutic approaches. Telocytes (TCs), a newly identified type of interstitial cells, have shown potential in tissue repair and angiogenesis, particularly through the release of exosomal microRNAs (miRNAs). This study investigated the role of TCs-derived exosomal miR-221 in ARDS. Our findings demonstrated that exosomes from LPS (lipopolysaccharide)-stimulated TCs significantly promoted angiogenesis, proliferation, and migration in mouse vascular endothelial cells (MVECs). These effects were mediated by miR-221, which downregulated E2F2 expression, an important regulator of endothelial cell functions. The JAK/STAT pathway played a crucial role in miR-221 production, with pathway inhibition reducing miR-221 levels and attenuating its pro-angiogenic effects. In vivo, TCs-derived exosomes reduced lung inflammation and tissue damage in ARDS mice, effects that were reversed by miR-221 inhibition. These results suggested that TCs-derived exosomes promoted angiogenesis and alleviated ARDS through the JAK/STAT-miR-221-E2F2 axis.