Circular RNA VMA21 ameliorates sepsis-associated acute kidney injury by regulating miR-9-3p/SMG1/inflammation axis and oxidative stress

J Cell Mol Med. 2020 Oct;24(19):11397-11408. doi: 10.1111/jcmm.15741. Epub 2020 Aug 22.

Abstract

Accumulating evidence suggests that circular RNAs have the abilities to regulate gene expression during the progression of sepsis-associated acute kidney injury. Circular RNA VMA21 (circVMA21), a recent identified circular RNA, could reduce apoptosis to alleviate intervertebral disc degeneration in rats and protect WI-38 cells from lipopolysaccharide-induced injury. However, the role of circVMA21 in sepsis-associated acute kidney injury (sepsis-associated AKI) is unknown. In this study, we first demonstrated that circVMA21 alleviated sepsis-associated AKI by reducing apoptosis and inflammation in rats and HK-2 cells. Additionally, to explore the molecule mechanism underlying the amelioration, after the bioinformatics analysis, we confirmed that miR-9-3p directly bound to circVMA21 by luciferase and RNA immunoprecipitation assay, and the effector protein of miR-9-3p was SMG1. Furthermore, the oxidative stress caused by sepsis-associated AKI was down-regulated by circVMA21. In conclusion, circVMA21 plays an important role in the regulating sepsis-associated AKI via adjusting miR-9-39/SMG1/inflammation axis and oxidative stress.

Keywords: SMG1; circVMA21; inflammation; miR-9-3p; oxidative stress.

MeSH terms

  • Acute Kidney Injury / complications*
  • Acute Kidney Injury / genetics
  • Animals
  • Apoptosis
  • Base Sequence
  • Cecum / pathology
  • Cell Line
  • Disease Models, Animal
  • Humans
  • Inflammation / genetics*
  • Ligation
  • Lipopolysaccharides
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oxidative Stress / genetics*
  • Protein Serine-Threonine Kinases / metabolism*
  • Punctures
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Rats, Wistar
  • Sepsis / complications*
  • Sepsis / genetics
  • Signal Transduction*

Substances

  • Lipopolysaccharides
  • MIRN9 microRNA, rat
  • MicroRNAs
  • RNA, Circular
  • Protein Serine-Threonine Kinases
  • Smg1 protein, rat