Knockout of Erbin promotes pyroptosis via regulating NLRP3/caspase-1/Gasdermin D pathway in sepsis-induced acute kidney injury

Clin Exp Nephrol. 2023 Sep;27(9):781-790. doi: 10.1007/s10157-023-02364-8. Epub 2023 Jun 13.

Abstract

Background: This study aims to investigate the correlation between Erbin and sepsis, and the role of Erbin on the pyroptosis pathway in acute kidney injury caused by sepsis and NLRP3/caspase-1/Gasdermin D pathway.

Methods: In the study, lipopolysaccharide (LPS) treatment or cecal ligation and puncture (CLP) surgery on mice were used to stimulate the in vitro and in vivo sepsis-induced renal injury model. The male C57BL/6 of wild-type mice (WT) and Erbin-knockout mice (Erbin-/-, EKO) were randomly divided into four groups (WT + Sham, WT + CLP, EKO + Sham, EKO + CLP). Inflammatory cytokine, renal function, pyroptotic cell numbers and the levels of protein and mRNA expression of pyroptosis, including the NLRP3 (all P < 0.05), were analyzed and found increase in Erbin-/- mice with CLP and LPS-induced HK-2 cells.

Results: The inhibited of Erbin shows a renal damaged effect by promoting NLRP3 inflammasome-mediated pyroptosis in SI-AKI.

Conclusion: This study demonstrated a novel mechanism by which Erbin regulates NLRP3 inflammasome-mediated pyroptosis in SI-AKI.

Keywords: Acute kidney injury; Erbin; Pyroptosis; Sepsis.

MeSH terms

  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / metabolism
  • Animals
  • Caspase 1 / metabolism
  • Caspase 1 / pharmacology
  • Gasdermins
  • Inflammasomes / metabolism
  • Inflammasomes / pharmacology
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Pyroptosis
  • Sepsis* / complications

Substances

  • Caspase 1
  • Gasdermins
  • Inflammasomes
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Erbb2ip protein, mouse