Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Genetic and Pharmacological Inhibition of CD36 Protects Against AIM2 PANoptosis During Renal Ischemia/Reperfusion Induced Acute Kidney Injury
49 Pages Posted: 5 Mar 2025
More...Abstract
Background: PANoptosis is a newly identified type of programmed cell death that extensively occur during the pathological process of infectious and inflammatory diseases. Although our previous literature mining research suggested that PANoptosis might occur in renal ischemia/reperfusion (I/R) injury, little experimental study has been reported on the existence of renal I/R induced PANoptosis. In this study, we proved PANoptosis take involved in the pathogenesis of acute kidney injury (AKI) and ameliorating mitochondrial oxidative stress and mtDNA escape by genetical and pharmacological inhibition of CD36 could protect mice from I/R induced PANoptosis.
Methods: We detected the active forms of three regulated cell death, that is pyroptosis, apoptosis and necroptosis protein markers simultaneously, which indicated the occurrence of PANoptosis in vivo and Co-immunoprecipitation (Co-IP) was performed to detect AIM2-PANoptosomes in vitro. In addition, we constructed two models AIM2 and CD36 KO mice to verify ameliorating I/R induced oxidative stress by inhibition of CD36 whether protect mice from I/R induced mitochondrial damage and AIM2-PANoptosis.
Findings: In this study, we found that knockdown of AIM2 inhibit I/R induced PANoptosis and had protective effects on I/R injury. In addition, I/R alters lipid metabolism and induced accumulation of lipid droplets accompany with the increased CD36 expression. By genetical and pharmacological inhibition of CD36 can significantly ameliorate I/R induced lipotoxicity, mtDNA leakage, and mtDNA dependent AIM2-PANoptosis.
Interpretation: PANoptosis participate in the pathogenesis of AKI and inhibition of CD36 mediated lipid metabolism dysfunction can ameliorate I/R induced PANoptosis, we provide preliminary experimental evidence for future study of this new type of regulated cell death in AKI.
Keywords: Keywords: Acute kidney injury, Ischemia/reperfusion injury, PANoptosis, CD36
Suggested Citation: Suggested Citation