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However, the role of histone lactylation in the development of sepsis\u2010associated acute kidney injury (SA\u2010AKI) remains unclear. Here, histone H3K18 lactylation (H3K18la) is elevated in SA\u2010AKI, which is reported in this study. Furthermore, this lactate\u2010dependent histone modification is enriched at the promoter of Ras homolog gene family member A (RhoA) and positively correlated with the transcription. Correction of abnormal lactate levels resulted in a reversal of abnormal histone lactylation at the promoter of RhoA. Examination of related mechanism revealed that histone lactylation promoted the RhoA\/Rho\u2010associated protein kinase (ROCK) \/Ezrin signaling, the activation of nuclear factor\u2010\u03baB (NF\u2010\u03baB), inflammation, cell apoptosis, and aggravated renal dysfunction. In addition, Ezrin can undergo lactylation modification. Multiple lactylation sites are identified in Ezrin and confirmed that lactylation mainly occurred at the K263 site. The role of histone lactylation is revealed in SA\u2010AKI and reportes a novel post\u2010translational modification in Ezrin. Its potential role in regulating inflammatory metabolic adaptation of renal proximal tubule epithelial cells is also elucidated. The results provide novel insights into the epigenetic regulation of the onset of SA\u2010AKI.<\/jats:p>","DOI":"10.1002\/advs.202307216","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T06:19:58Z","timestamp":1716185998000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":142,"title":["Histone H3K18 and Ezrin Lactylation Promote Renal Dysfunction in Sepsis\u2010Associated Acute Kidney Injury"],"prefix":"10.1002","volume":"11","author":[{"given":"Jiao","family":"Qiao","sequence":"first","affiliation":[{"name":"Institute of Medical Technology Peking University Health Science Center  Beijing 100191 China"},{"name":"Department of Laboratory Medicine Peking University Third Hospital  Beijing 100191 China"},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine Peking University Third Hospital  Beijing 100191 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