Lipopolysaccharide-induced active telocyte exosomes alleviate lipopolysaccharide-induced vascular barrier disruption and acute lung injury via the activation of the miRNA-146a-5p/caspase-3 signaling pathway in endothelial cells

Abstract

Background: Lipopolysaccharide (LPS)-induced apoptosis of lung microvascular endothelial cells (ECs) is the main reason of lung edema and acute lung injury (ALI) in septic conditions. Telocytes (TCs) are a distinct type of interstitial cells found around the lung microvasculature, which may protect ECs through the release of shed vesicles. However, whether TCs protect against LPS-induced EC apoptosis and ALI has not been determined. Methods: The protective effects of TCs on ECs were assessed in vitro using transwell assays and flow cytometry, and in vivo using an LPS-induced mouse ALI model. RNA sequencing was used to identify miRNA-146a-5p as a key component of TC-derived exosomes. The functions of miRNA-146a-5p were further evaluated by western blotting, flow cytometry, and transendothelial electrical resistance measurements. Results: We demonstrated that LPS stimulation induced the secretion of active exosomes from TCs, which inhibited LPS-mediated apoptosis of ECs and reduced ALI in mice. Moreover, miRNA-146a-5p was identified as the main bioactive molecule in TC-derived exosomes, capable of inhibiting LPS-induced caspase-3 activation and apoptosis in ECs. Conclusions: Our results indicate that TCs effectively prevent LPS-induced EC apoptosis and ALI through the release of exosomes, with subsequent activation of the miRNA-146a-5p/caspase-3 signaling pathway in ECs.