Inhibition of sepsis-induced acute kidney injury via the circITCH-miR-579-3p-ZEB2 axis

Environ Toxicol. 2023 Jun;38(6):1217-1225. doi: 10.1002/tox.23682. Epub 2023 Mar 31.

Abstract

Circular RNAs (circRNAs) are linked to the regulation of sepsis-induced acute kidney injury (AKI). However, the function of circITCH in the development of sepsis-induced AKI is still unclear. The levels of circITCH, miR-579-3p and ZEB2 were examined by real-time PCR and immunoblotting. Then, the roles of circITCH in cell viability, apoptosis, and inflammation in lipopolysaccharide (LPS)-treated HK-2 cells were evaluated. The further mechanism was investigated using rescue assays. CircITCH was downregulated in septic AKI patients and LPS-triggered HK-2 cells. CircITCH overexpression restored cell viability in LPS-treated HK-2 cells and restrained apoptosis and inflammatory cytokine production. CircITCH negatively regulated miR-579-3p, thereby upregulating ZEB2 expression. Taken together, circITCH alleviates LPS-induced HK-2 cell injury by regulating miR-579-3p/ZEB2 signal axis, which provides a theoretical basis for AKI therapy.

Keywords: acute kidney injury; circRNA; inflammation; lipopolysaccharide.

MeSH terms

  • Acute Kidney Injury* / genetics
  • Apoptosis / genetics
  • Humans
  • Lipopolysaccharides / pharmacology
  • MicroRNAs* / genetics
  • Sepsis* / complications
  • Sepsis* / genetics
  • Zinc Finger E-box Binding Homeobox 2 / genetics

Substances

  • Lipopolysaccharides
  • MicroRNAs
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • MIRN579 microRNA, human