Histone H3K18 and Ezrin Lactylation Promote Renal Dysfunction in Sepsis‐Associated Acute Kidney Injury
Abstract: Histone lactylation is a metabolic stress‐related histone modification. However, the role of histone lactylation in the development of sepsis‐associated acute kidney injury (SA‐AKI) remains unclear. Here, histone H3K18 lactylation (H3K18la) is elevated in SA‐AKI, which is reported in this study. Furthermore, this lactate‐dependent 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‐associated protein kinase (ROCK)/Ezrin signaling, the activation of nuclear factor‐κB (NF‐κB), 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‐AKI and reportes a novel post‐translational 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‐AKI.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Histone H3K18 and Ezrin Lactylation Promote Renal Dysfunction in Sepsis‐Associated Acute Kidney Injury ; day:20 ; month:05 ; year:2024 ; extent:18
Advanced science ; (20.05.2024) (gesamt 18)
- Creator
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Qiao, Jiao
Tan, Yuan
Liu, Hongchao
Yang, Boxin
Zhang, Qian
Liu, Qi
Sun, Wenyuan
Li, Zhongxin
Wang, Qingchen
Feng, Weimin
Yang, Shuo
Cui, Liyan
- DOI
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10.1002/advs.202307216
- URN
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urn:nbn:de:101:1-2405201419050.861874573549
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:54 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Qiao, Jiao
- Tan, Yuan
- Liu, Hongchao
- Yang, Boxin
- Zhang, Qian
- Liu, Qi
- Sun, Wenyuan
- Li, Zhongxin
- Wang, Qingchen
- Feng, Weimin
- Yang, Shuo
- Cui, Liyan
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