Endothelial progenitor cell-derived extracellular vesicles protect from complement-mediated mesangial injury in experimental anti-Thy1.1 glomerulonephritis

摘要: Background Endothelial progenitor cells (EPCs) are known to induce tissue repair by paracrine mechanisms including the release of growth factors and extracellular vesicles (EVs), nanoparticles able carry proteins genetic information target cells. The aim this study was evaluate whether EVs derived from EPCs may protect complement-mediated mesangial injury in experimental anti-Thy1.1 glomerulonephritis. Methods were isolated serial ultracentrifugation supernatants cultured human characterized for their protein RNA content. In vivo, injected i.v. rat model mesangiolytic glomerulonephritis evaluating renal function, proteinuria, complement activity histological lesions. vitro, biological effects EPC-derived studied incubated with antibody or serum as source. Results After injection Thy1.1-treated rats, localized within injured glomeruli inhibited cell activation, leucocyte infiltration apoptosis, decreased increased haemolytic (CH50) ameliorated function. EV treatment intraglomerular deposition membrane attack complex (MAC C5b-9) expression smooth muscle actin preserved endothelial antigen RECA-1 podocyte marker synaptopodin. protective effect significantly reduced pre-treatment a high dose RNase (1 U/mL), suggesting key role EV-carried RNAs these mechanisms. Indeed, contained different mRNAs coding several anti-apoptotic molecules inhibitors Factor H, CD55 CD59 related proteins. vitro experiments aimed investigate protection indicated that transferred antibody/complement-induced apoptosis C5b-9/C3 deposition. Conclusions exert Thy1.1 inhibition antibody-