Therapeutic potential of endothelial progenitor cell-derived exosomal miRNA-31 in alleviating septic peritonitis via E-selectin inhibition.

Abstract

Septic peritonitis (SP) is a severe infectious complication associated with high morbidity and mortality. The role of microRNAs, particularly endothelial progenitor cell-derived exosomal miRNA-31 (EPC-ExosmiR-31), in modulating inflammatory pathways in SP has garnered scholars' attention. However, its precise role and mechanism of action remain inadequately explored. Serum levels of miRNA-31 (miR-31) and soluble E-selectin (sSELE) were measured in patients with SP and healthy controls using qRT-PCR and ELISA. A colon ascendens stent peritonitis (CASP) mouse model was employed to replicate SP, and an in vitro sepsis model was induced via lipopolysaccharide (LPS) stimulation of mouse venous endothelial cells. The effects of EPC-ExosmiR-31 on cellular proliferation, apoptosis, and inflammatory markers were assessed through Giemsa and hematoxylin and eosin staining, qRT-PCR, Western blotting, and dual-luciferase reporter assay. Statistical analysis was conducted to evaluate the correlation among miR-31, sSELE, and sepsis severity. Patients with SP exhibited significantly lower serum miR-31 levels and elevated sSELE levels compared with healthy controls, and these changes were correlated with the severity of sepsis. In the CASP mouse model, extensive neutrophilic infiltration and inflammatory tissue damage were found in the lungs, liver, and colon. EPC-ExosmiR-31 administration significantly mitigated these effects by reducing SELE, caspase-3, and Bax expression levels, while increasing Bcl-2 expression level. In vitro, miR-31 enhanced cell proliferation and inhibited apoptosis in LPS-treated endothelial cells. The dual-luciferase reporter assay confirmed that miR-31 could directly target SELE. EPC-ExosmiR-31 alleviated SP by targeting SELE, thereby reducing endothelial dysfunction and systemic inflammation, reflecting a promising therapeutic approach for managing SP.