MiR-361-3p mitigates lipopolysaccharide-induced inflammation and acute kidney injury by post-transcriptional repression of the myeloid differential protein 88/nuclear factor-kB pathway

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IntroductionmicroRNAs (miRs) have been reported to contribute to sepsis-associated acute kidney injury (AKI). Herein, the roles of miR-361-3p and the underlying mechanism were investigated in lipopolysaccharide (LPS)-induced podocyte injury.Material and methodsAfter podocyte exposure to LPS (1 mg/ml), proinflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA); cell apoptosis was evaluated by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. In vivo septic mice, miR-361-3p agonist, agomir-miR-361-3p (20 nM/0.1 ml), was used to treat LPS-induced AKI.ResultsOur findings reveal a significant elevation of proinflammatory cytokine production, in addition to the development of podocyte apoptosis after LPS stimulation. However, knockdown of myeloid differentiation primary response protein 88 (MyD88) significantly prevents podocyte death and suppresses the inflammatory response in LPS-stimulated podocytes. More importantly, MyD88 is a direct target of miR-361-3p that can counteract LPS-induced inflammation and podocyte dysfunction via post-transcriptional repression of MyD88. The rescue experiments provide a confrontational phenomenon between miR-361-3p and MyD88 in LPS-stimulated podocytes, reflecting that overexpression of MyD88 neutralizes the protective effect of miR-361-3p on LPS-stimulated podocyte inflammation and apoptosis. Our results also demonstrate that miR-361-3p agonist alleviates LPS-induced renal injury and activation of the toll-like receptor 4 (TLR4)/MyD88/nuclear factor-kappa B (NF-κB) axis.ConclusionsmiR-361-3p suppresses LPS-induced inflammation, podocyte apoptosis and AKI by targeting the MyD88/NF-κB pathway. This may provide a novel strategy for the treatment of sepsis-associated AKI.