Platelet exosome-derived miR-223-3p regulates pyroptosis in the cell model of sepsis-induced acute renal injury by targeting mediates NLRP3

Background The present study investigated that the roles and mechanisms of platelet-derived exosomes in sepsis-induced acute renal injury. Methods The blood samples of septic patients and healthy controls were collected for clinical examination. The plasma level of miR-223-3p and NLRP3 mRNA were analyzed by qRT-PCR and the serum IL-1β and creatinine levels were quantified by ELISA(Enzyme-linked immunosorbent assay). C57BL/6 mice injected with LPS(lipopolysaccharide) were employed as the animal model for sepsis-induced acute renal injury. Human coronary artery endothelial cells(HCAECs) were treated with TNF-α as a cellular model for sepsis-induced endothelial damages. Results The number of PMP(platelet-derived microparticles) in patients with sepsis was increased. The level of miR-223-3p in the platelet exosomes isolated from the serum sample in patients with sepsis was significantly lower than that of the healthy controls. The level of miR-223-3p was also decreased in the platelet exosomes of mouse model with sepsis-induced acute renal injury. Downregulating miR-223-3p promoted sepsis-induced acute renal injury in mice model, while the administration of miR-223-3p reduced the inflammation in endothelial cells of sepsis-induced acute renal injury. NLRP3 (NLR Family Pyrin Domain Containing 3) was identified as one target of miR-223-3p in the platelet exosomes of sepsis-induced acute kidney injury. MiR-223-3p attenuated NLRP3-induced pyroptosis in endothelial cell model of sepsis-induced acute kidney injury. Conclusion In summary, platelet exosome-derived miR-223-3p regulates NLRP3 inflammasome and pyroptosis of endothelial cells in model of sepsis-induced acute renal