ZBP1 Promotes RIPK1-Dependent Apoptosis in Aristolochic Acid Nephropathy - PubMed
3 hours ago
- #Nephropathy
- #Aristolochic Acid
- #Apoptosis
- Aristolochic acid nephropathy (AAN) is a progressive kidney disease leading to end-stage renal disease (ESRD).
- Z-DNA-binding protein 1 (ZBP1) is identified as a key mediator of AA-induced kidney injury.
- ZBP1 knockout or mutation protects against AA-induced renal dysfunction, apoptosis, and inflammation.
- AAI induces mitochondrial oxidative stress and release of Z-conformation mitochondrial DNA (mtDNA), recognized by ZBP1.
- ZBP1 promotes RHIM-dependent interaction with RIPK1, leading to caspase-8 activation and apoptotic cell death.
- ZBP1-mediated cell death is abolished by RIPK1 kinase inhibition or mutation, but unaffected by Ripk3 or Mlkl deletion.
- The findings suggest a novel ZBP1-RIPK1-caspase-8 signaling axis in AAN, offering potential therapeutic targets.