Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review
Abstract 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 mec...
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2025-05-01
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| Series: | BMC Nephrology |
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| Online Access: | https://doi.org/10.1186/s12882-025-04179-z |
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| author | Lili Liu Saisai Ni Lianna Zhang Yingying Chen Mengqi Xie Xiaojing Huang |
| author_facet | Lili Liu Saisai Ni Lianna Zhang Yingying Chen Mengqi Xie Xiaojing Huang |
| author_sort | Lili Liu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-4916b32ec60340eb87f39caff9d2429c |
| institution | DOAJ |
| issn | 1471-2369 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj-art-4916b32ec60340eb87f39caff9d2429c2025-08-20T03:08:40ZengBMCBMC Nephrology1471-23692025-05-012611810.1186/s12882-025-04179-zMolecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative reviewLili Liu0Saisai Ni1Lianna Zhang2Yingying Chen3Mengqi Xie4Xiaojing Huang5Department of Emergency MedicineDepartment of Emergency MedicineDepartment of Emergency MedicineDepartment of Emergency MedicineDepartment of Emergency MedicineDepartment of Emergency MedicineAbstract 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.https://doi.org/10.1186/s12882-025-04179-zSepsisAcute kidney injuryDNA methylationEpigeneticsInflammationBiomarkers |
| spellingShingle | Lili Liu Saisai Ni Lianna Zhang Yingying Chen Mengqi Xie Xiaojing Huang Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review BMC Nephrology Sepsis Acute kidney injury DNA methylation Epigenetics Inflammation Biomarkers |
| title | Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review |
| title_full | Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review |
| title_fullStr | Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review |
| title_full_unstemmed | Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review |
| title_short | Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review |
| title_sort | molecular insights and clinical implications of dna methylation in sepsis associated acute kidney injury a narrative review |
| topic | Sepsis Acute kidney injury DNA methylation Epigenetics Inflammation Biomarkers |
| url | https://doi.org/10.1186/s12882-025-04179-z |
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