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Targeting VDAC1-dependent mtDNA release attenuates fibroblast innate immune activation and vitiligo pathogenesis - PubMed

4 hours ago
  • #Oxidative Stress
  • #Vitiligo
  • #Fibroblasts
  • Vitiligo is a chronic depigmentary disorder initiated by oxidative stress, leading to melanocyte destruction.
  • Dermal fibroblasts play a key role in vitiligo pathogenesis by releasing mitochondrial DNA (mtDNA) under oxidative stress.
  • Oxidative stress in normal human dermal fibroblasts (NHDFs) induces VDAC1-dependent mtDNA release without apoptosis.
  • Released mtDNA activates the cGAS-STING pathway and NLRP3 inflammasome, driving inflammatory cytokine expression.
  • Pharmacological inhibition of VDAC1 oligomerization with VBIT-4 prevents mtDNA leakage and attenuates inflammation.
  • Targeting VDAC1-mtDNA-cGAS-STING axis in fibroblasts shows promise for vitiligo treatment.