Long non-coding RNA XIST alleviates sepsis-induced acute kidney injury through inhibiting inflammation and cell apoptosis via regulating miR-155-5p/WWC1 axis.

Abstract

Sepsis is characterized by a severe inflammatory response throughout the whole body and can induce acute kidney injury (AKI). This research aimed to investigate the regulatory mechanisms underlying miR-155-5p in sepsis-induced AKI. CLP-treated mice were used as an in vivo model of sepsis-induced AKI, and LPS-treated HK-2 and TCMK-1 cells were used as in vitro models. Bioinformatics analyses and mechanistic assays were utilized to reveal the relationships between molecules. H&E staining was used to reveal morphological changes in kidney tissues. ELISAs were conducted to detect the concentrations of proinflammatory cytokines. We discovered that miR-155-5p was prominently upregulated in sepsis-induced AKI in vivo and in vitro. MiR-155-5p inhibition alleviated kidney injury in mice. Moreover, WWC1 served as a direct target of miR-155-5p and was negatively regulated by miR-155-5p. WWC1 upregulation inhibited the productions of inflammatory cytokines and suppressed apoptosis in vivo and in vitro. In addition, rescue assays demonstrated that WWC1 knockdown counteracted the inhibitory effect of anti-miR-155-5p on inflammation and apoptosis. Moreover, miR-155-5p could bind to XIST. XIST expression was downregulated in LPS-stimulated HK-2 and TCMK-1 cells. XIST could negatively regulate miR-155-5p expression and positively regulate WWC1 expression. Rescue assays revealed that miR-155-5p overexpression significantly reversed the suppressive effects of XIST upregulation on inflammation and apoptosis. In conclusion, our study revealed that the XIST/miR-155-5p/WWC1 axis modulated sepsis-induced AKI progression, providing promising insight into therapeutic targets for sepsis-induced AKI.