Pan-PPAR agonist bezafibrate alleviates psoriasis by suppressing LCN2-dependent ferroptosis - PubMed
3 months ago
- #psoriasis
- #lipid-metabolism
- #ferroptosis
- Psoriasis is a chronic inflammatory skin disease linked to keratinocyte hyperproliferation and immune dysregulation.
- Ferroptosis, an iron-dependent cell death process driven by lipid peroxidation, plays a key role in psoriasis pathogenesis.
- Lipocalin-2 (LCN2), an iron-binding protein elevated in psoriasis, may regulate ferroptosis.
- Bezafibrate (BEZ), a pan-PPAR agonist, was investigated for its potential to alleviate psoriasis by targeting LCN2-mediated ferroptosis.
- Psoriatic lesions showed ferroptosis activation, including reduced GPX4, increased ACSL4 and ALOX12, elevated lipid peroxidation, and GSH depletion.
- GPX4 knock-in mice showed improved psoriatic features, confirming ferroptosis involvement.
- BEZ treatment reduced disease severity, epidermal thickening, and keratinocyte proliferation while restoring redox balance.
- BEZ reversed pro-ferroptotic lipid accumulation (e.g., ceramides, PE species) and downregulated arachidonic acid metabolism.
- BEZ suppressed LCN2 expression, and LCN2 overexpression negated BEZ's protective effects against ferroptosis and inflammation.
- BEZ alleviates psoriasis by inhibiting ferroptosis via LCN2 suppression and lipid metabolic reprogramming, highlighting pan-PPAR activation as a therapeutic strategy.