E3 Ubiquitin Ligase FBXO32 Promotes LPS-Induced Cardiac Injury by Regulating ANXA1/PI3K/AKT Signaling

Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis. Therefore, understanding SIC pathogenesis and developing new therapeutic targets are of great significance. This study investigated the role of F-box-only protein 32 (FBXO32) in SIC pathogenesis. LPS-induced cardiac injury models were established in rats and H9c2 cells using lipopolysaccharide. The effects of FBXO32 on myocardial apoptosis and mitochondrial structure and function were determined using electron microscopy, reactive oxygen species detection, and JC-1 staining. The molecular mechanism was elucidated using western blotting and co-immunoprecipitation. The results showed elevated FBXO32 expression in both in vivo and in vitro LPS-induced cardiac injury models. Fbxo32 knockdown alleviated apoptosis and mitochondrial and cardiac dysfunction. Mechanistic analysis revealed that FBXO32 promoted ubiquitination and degradation of annexin A1 (ANXA1), inhibiting the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) pathways. Rescue experiments demonstrated that Anxa1 knockdown reversed the effects of Fbxo32 knockdown. This study suggests that FBXO32 exacerbates LPS-induced cardiac injury progression by mediating ANXA1 ubiquitination and inhibiting the PI3K/AKT signaling pathway.