Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review

作者：Lili Liu, Saisai Ni, Lianna Zhang, Yingying Chen, Mengqi Xie, Xiaojing Huang · 发表于：BMC Nephrology · 年份：2025 · DOI：10.1186/s12882-025-04179-z · 被引用次数：10 · 研究领域：Palliative Care and End-of-Life Issues、Immune responses and vaccinations、Dialysis and Renal Disease Management

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...