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CYBB-Mediated Ferroptosis Drives Podocyte Injury in Lupus Nephritis and Represents a Therapeutic Target - PubMed

5 hours ago
  • #podocyte injury
  • #lupus nephritis
  • #ferroptosis
  • CYBB-mediated ferroptosis is identified as a key driver of podocyte injury in lupus nephritis (LN).
  • Ferroptosis markers (iron overload, lipid peroxidation, glutathione depletion, GPX4 downregulation) were observed in MRL/lpr mice, leading to podocyte loss and proteinuria.
  • Ferrostatin-1 (Fer-1) treatment significantly improved renal pathology and preserved podocyte integrity.
  • Bioinformatic analysis identified CYBB as a ferroptosis-related hub gene upregulated in LN, correlating with renal dysfunction and oxidative injury.
  • CYBB overexpression enhanced ROS generation and ferroptotic podocyte damage, while CYBB knockdown or Fer-1 reversed these effects.
  • Both pharmacological and genetic inhibition of CYBB mitigated ferroptosis, preserved podocyte integrity, and improved renal function, highlighting CYBB as a promising therapeutic target in LN.