OTUB1 regulation of ferroptosis and the protective role of ferrostatin-1 in lupus nephritis.

ABSTRACT: Lupus nephritis (LN) is a prevalent and severe manifestation of systemic lupus erythematosus (SLE), leading to significant morbidity and mortality. OTUB1, a deubiquitinating enzyme, has emerged as a potential therapeutic target due to its role in cellular protection and regulation of ferroptosis, a form of cell death linked to LN. Our study revealed significantly reduced OTUB1 expression in the glomeruli of LN patients and podocytes, correlated with disease severity. CRISPR/Cas9-mediated OTUB1 knockout in podocytes resulted in pronounced injury, indicated by decreased levels of nephrin and podocin. Ferrostatin-1 treatment effectively mitigated this injury, restoring SLC7A11 expression and significantly reducing MDA levels, Fe²⁺ levels, BODIPY C11 expression, and normalized cyste

SUBMITTER: Liu C 

PROVIDER: S-EPMC11538433 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature