Kaempferol functionally reprograms CD47 signaling to promote cytoprotection and attenuate oxeiptosis in severe acute pancreatitis - PubMed
3 hours ago
- #CD47 Signaling
- #Oxeiptosis
- #Kaempferol
- Kaempferol (KA) protects against severe acute pancreatitis (SAP) by reprogramming CD47 signaling to reduce pancreatic acinar cell (PAC) death, specifically by attenuating oxeiptosis.
- CD47 upregulation in SAP promotes PAC death through the KEAP1/PGAM5/AIFM1 oxeiptosis pathway; its knockout reduces death, but KA's protection is CD47-dependent.
- KA binds allosterically to the CD47 ectodomain, stabilizing the CD47-UBQLN1 complex and shifting signaling from Gαi-mediated death to Gβγ/ERK/NRF2 survival pathways.
- The study uses multi-omics, biophysical assays, and genetic models to identify CD47 as KA's direct target, revealing anti-oxeiptosis as a novel pharmacological activity of KA.
- Findings position KA as a promising SAP therapy candidate and highlight the CD47-oxeiptosis axis as a therapeutic target, adding to KA's known anti-inflammatory effects.