Background
Acute kidney injury (AKI) is a severe complication of sepsis, and is strongly correlated with MicroRNAs (miRNAs). However, the mechanism of miR-22 on sepsis-induced AKI is not clearly understood. The study aimed to explore the role and mechanism of miR-22 on AKI.
Conclusion
miR-22 can inhibit the inflammatory response, target the HMGB1, and inhibit the HMGB1/TLR4/NF-kB pathway, to attenuate the sepsis-induced AKI, which indicates that miR-22 may serve as a potential treatment target in sepsis-induced AKI.
Methods
The AKI models were established by cecal ligation and puncture (CLP) surgery in SD rats and lipopolysaccharide (LPS) induction in HBZY-1 cells. In AKI rats, the content of serum creatinine (SCr) and blood urea nitrogen (BUN) were detected. Kidney tissues were pathologically examined by H&E and PAS staining. The LPS-induced HBZY-1 cells were transfected with mimics miR-22, si-HMGB1, or oe-HMGB1. miR-22 and HMGB1 expression was detected in vivo and in vitro. In transfected cells, HMGB1/TLR4/NF-κB pathway-related protein expressions were measured by Western blot. The relationship between miR-22 and HMGB1 was assessed by a dual-luciferase gene report. Inflammatory cytokine levels in serum and cells were assessed by ELISA.
Results
In AKI rats, kidney injury was observed, accompanied by the down-regulated miR-122 expression and up-regulated HMBG1 expression. The dual-luciferase report found miR-22-3p could targetly regulate HMBG1. Furthermore, both in vitro and in vivo experiments revealed that the releases of inflammatory cytokine were increased after AKI modeling, but the situation was reversed by mimics miR-22 or si-HMGB1 in vitro. In HBZY-1 cells, mimics miR-22 could suppress LPS-induced overexpression of HMGB1/TLR4/NF-κB signaling pathway-related proteins. However, the oe-HMGB1 addition reversed the effect of mimics miR-22.