KLF15 reduces the level of apoptosis in mouse liver induced by sepsis by inhibiting p38MAPK/ERK1/2 signaling pathway

Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10819-10828. doi: 10.26355/eurrev_202010_23444.


Objective: Sepsis-induced acute liver injury (ALI) involves multiple systems in the body. The disease is acute and critical, with various symptoms, including extensive necrosis of liver cells. There is currently no effective treatment to deal with ALI in a timely manner. This study verified the therapeutic effect of Krüppel-like factor 15 (KLF15) on ALI by studying its anti-apoptotic effect on the liver.

Materials and methods: We induced ALI in mice with lipopolysaccharide (LPS)/D-galactosamine (D-GaIN). Recombinant mouse KLF15 was used to treat mice to examine the protective effects of KLF15 on mouse liver and the effects of apoptosis-related molecules. In addition, we cultured Kupffer cells and determined the anti-inflammatory and anti-apoptotic effects of KLF15 and its mechanism by overexpressing KLF15.

Results: Exogenous KLF15 effectively reduced the levels of TIBL, ALT, AST, and inflammatory factors (COX-2, MCP-1, IL-1β, and TNF-α) in mouse serum. The results of HE staining also demonstrate that KLF15 improves the morphology of liver tissue. In addition, the expression of KLF15 in LPS-induced Kupffer cells was significantly reduced and KLF15 increased the viability of Kupffer cells and decreased the level of inflammation in Kupffer cells. In both in vivo and in vitro experiments, KLF15 reduced the level of apoptosis in hepatocytes or Kupffer cells and inhibited the activity of the p38MAPK/ERK1/2 signaling pathway.

Conclusions: KLF15 reduces the apoptosis and inflammation levels of liver and Kupffer cells by inhibiting the p38MAPK/ERK1/2 signaling pathway and alleviates LPS/D-GaIN-induced ALI.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Survival
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury
  • Galactosamine
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Lipopolysaccharides
  • Liver / metabolism*
  • Liver / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Sepsis / chemically induced
  • Sepsis / metabolism*
  • Sepsis / pathology
  • Signal Transduction*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Klf15 protein, mouse
  • Kruppel-Like Transcription Factors
  • Lipopolysaccharides
  • Galactosamine
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases