Open AccessLong non‐coding RNA XIST alleviates sepsis‐induced acute kidney injury through inhibiting inflammation and cell apoptosis via regulating miR ‐155‐5p/ WWC1 axis
Author(s) -
Wang Lei,
Cao QiuMei
Publication year - 2022
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1002/kjm2.12442
Subject(s) - gene knockdown , downregulation and upregulation , xist , proinflammatory cytokine , inflammation , medicine , apoptosis , in vivo , sepsis , long non coding rna , cancer research , microbiology and biotechnology , immunology , biology , gene , biochemistry , x chromosome , x inactivation
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.