Key points are not available for this paper at this time.
Sepsis-induced acute kidney injury (S-AKI) is a life-threatening complication of sepsis, marked by dysregulated inflammation, metabolic derangements, and immune dysfunction, driving high mortality. Its multifactorial pathogenesis increasingly implicates DNA methylation-a core epigenetic mechanism-as a critical disease modulator. This review synthesizes current knowledge of DNA methylation in S-AKI, covering molecular mechanisms, cellular dysfunction, and translational potential. In immune cells, sepsis-induced aberrant DNA methylation promotes hypomethylation of pro-inflammatory genes and hypermethylation of anti-inflammatory loci, exacerbating cytokine storms and immunosuppression. In renal tubular epithelial cells, abnormal methylation disrupts apoptosis, oxidative stress responses, and mitochondrial bioenergetics, impairing repair and accelerating S-AKI progression. Renal vascular endothelial cells exhibit methylation-dependent dysregulation of vasoactive and inflammatory pathways, compromising microvascular homeostasis and renal hemodynamics. DNA methylation signatures offer promise as early S-AKI biomarkers, with cell-type-specific patterns reflecting severity, injury, and prognosis. Targeting DNA methyltransferases with epigenetic modifiers represents a novel therapy, though challenges arise from sepsis's complex epigenetic landscape-bidirectional methylation changes, histone crosstalk, and context-dependent responses. A key paradox lies in DNA methylation's dual traits: stability underpinning biomarker reliability and plasticity enabling dynamic inflammatory adaptation, yet introducing therapeutic heterogeneity. Future research should prioritize dissecting cell-specific methylation mechanisms, integrating multi-omics to identify epigenetic subnetworks, and developing real-time monitoring tools for precision diagnosis and tailored interventions. Advancing these frontiers may translate epigenetic insights into transformative strategies to improve outcomes for this devastating condition.
Liu et al. (Thu,) studied this question.