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Background <p>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.</p> Methods <p>SA-AKI cell model was constructed in HK2 cells by LPS treatment. Levels of KLF2, <i>lncRNA GAS6-AS2</i> and GOLPH3 were determined by RT-qPCR and WB. After upregulating KLF2 expression, cell viability and cytotoxicity were assessed, <i>KIM-1</i> 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 <i>lncRNA GAS6-AS2</i> promoter was analyzed. The binding relationships among <i>lncRNA GAS6-AS2</i>, ELAVL2 and <i>GOLPH3</i> were analyzed by RIP. GOLPH3 mRNA stability was assessed. The role of <i>lncRNA GAS6-AS2</i>/GOLPH3 in KLF2-regulated cell injury was analyzed through combined experiment.</p> Results <p>KLF2 expression was decreased, while <i>lncRNA GAS6-AS2</i> and GOLPH3 expressions were increased. In LPS-treated HK2, KLF2 overexpression elevated cell viability, inhibited LDH activity, reduced apoptosis, and decreased <i>KIM-1</i>, <i>NGAL</i>, inflammation, and oxidative stress levels. KLF2 bound to and inhibited the <i>lncRNA GAS6-AS2</i> promoter, while <i>lncRNA GAS6-AS2</i> interacted with ELAVL2 and indirectly stabilized GOLPH3. <i>LncRNA GAS6-AS2</i> or GOLPH3 overexpression attenuated the protective effects of KLF2 overexpression on LPS-induced cellular injury.</p> Conclusion <p>KLF2 binds to and inhibits the transcription of <i>lncRNA GAS6-AS2</i>, which in turn reduces the ELAVL2-mediated stabilization of GOLPH3 mRNA, ultimately alleviating cellular injury in SA-AKI.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Wei Feng,
  • Yu-Feng Zhu,
  • Kai-Yuan Li,
  • Xiao-Shuang Xu,
  • Bo-Yu Zhang,
  • Jian Zhou

摘要

Background

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.

Methods

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.

Results

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.

Conclusion

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.