KLF2 alleviates sepsis-induced acute kidney injury via the lncRNA GAS6-AS2/GOLPH3 axis

Sepsis-associated acute kidney injury (SA-AKI) is a leading cause of organ failure with high morbidity and mortality. We aimed to investigate the effect and mechanism of KLF2 on SA-AKI cell model, trying to provide novel knowledge for AKI treatment. SA-AKI cell model was constructed in HK2 cells by LPS treatment. Levels of KLF2, lncRNA GAS6-AS2 and GOLPH3 were determined by RT-qPCR and WB. After upregulating KLF2 expression, cell viability and cytotoxicity were assessed, KIM-1 and NGAL mRNA levels were detected by RT-qPCR, inflammation level was detected by ELISA, cell apoptosis was detected by flow cytometry, and ROS, MDA, and GSH were tested by kits. The binding of KLF2 to the lncRNA GAS6-AS2 promoter was analyzed. The binding relationships among lncRNA GAS6-AS2, ELAVL2 and GOLPH3 were analyzed by RIP. GOLPH3 mRNA stability was assessed. The role of lncRNA GAS6-AS2/GOLPH3 in KLF2-regulated cell injury was analyzed through combined experiment. KLF2 expression was decreased, while lncRNA GAS6-AS2 and GOLPH3 expressions were increased. In LPS-treated HK2, KLF2 overexpression elevated cell viability, inhibited LDH activity, reduced apoptosis, and decreased KIM-1, NGAL, inflammation, and oxidative stress levels. KLF2 bound to and inhibited the lncRNA GAS6-AS2 promoter, while lncRNA GAS6-AS2 interacted with ELAVL2 and indirectly stabilized GOLPH3. LncRNA GAS6-AS2 or GOLPH3 overexpression attenuated the protective effects of KLF2 overexpression on LPS-induced cellular injury. KLF2 binds to and inhibits the transcription of lncRNA GAS6-AS2, which in turn reduces the ELAVL2-mediated stabilization of GOLPH3 mRNA, ultimately alleviating cellular injury in SA-AKI.