Narciclasine attenuates sepsis-associated acute kidney injury through the ESR1/S100A11 axis

Funct Integr Genomics. 2025 Jan 14;25(1):13. doi: 10.1007/s10142-024-01513-w.

Abstract

Narciclasine (Ncs) was effective in sepsis management due to its antioxidant properties. The present study dissected the protective effects of Ncs against sepsis-associated acute kidney injury (SA-AKI) and the molecular mechanisms. The SA-AKI mice were developed using cecum ligation and puncture and pretreated with Ncs and adenoviruses. Human renal microvascular endothelial cells (RMECs) were induced with LPS and treated with Ncs. Ncs alleviated proximal tubular dilatation, interstitial widening, and necrosis in renal tissues and reduced the renal injury marker and pro-inflammatory cytokine levels in the serum of SA-AKI mice. Ncs promoted the expression of ZO-1, VE-cadherin, and CD31 and the activities of SOD, GSH-Px, and CAT, and inhibited the levels of pro-inflammatory cytokines, and apoptosis rate in LPS-treated RMECs. Estrogen receptor 1 (ESR1) was a target protein of Ncs, and S100 calcium-binding protein A11 (S100A11) was a target of the transcription factor ESR1. Ncs blocked transcription of S100A11 by inhibiting ESR1. Silencing of S100A11 overturned the deteriorating effects of ESR1 overexpression on SA-AKI progression in vivo and RMEC injury in vitro. These findings suggest that Ncs may ameliorate SA-AKI by repressing the ESR1/S100A11 signaling, providing a novel perspective for research on SA-AKI.

Keywords: ESR1; Narciclasine; Renal microvascular endothelial cells; S100A11; Sepsis-associated acute kidney injury.

MeSH terms

  • Acute Kidney Injury* / drug therapy
  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / genetics
  • Acute Kidney Injury* / metabolism
  • Amaryllidaceae Alkaloids* / pharmacology
  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Estrogen Receptor alpha* / genetics
  • Estrogen Receptor alpha* / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phenanthridines* / pharmacology
  • Sepsis* / complications
  • Sepsis* / drug therapy
  • Signal Transduction / drug effects

Substances

  • Phenanthridines
  • narciclasine
  • Amaryllidaceae Alkaloids
  • Estrogen Receptor alpha
  • Esr1 protein, mouse
  • Cytokines