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Lactylation: A central metabolic-epigenetic driver of sepsis-associated acute kidney injury.

Created on 28 Aug 2026

Authors

Yuqiu Wang, Yan Huang, Jiang Du, Hang Wen, Xintong Shi, Jian Zhao, Yuxin Chen, Ying Zhao, Jianwei Wang, Haibo Wang, Pingbo Xu

Published in

Molecular biology reports. Volume 53. Issue 1. Aug 27, 2026. Epub Aug 27, 2026.

Abstract

Sepsis-associated acute kidney injury is a lethal complication with limited therapeutic options. The discovery of protein lactylation, a novel modification where lactate modifies lysine residues, has redefined lactate from a metabolic waste product to a key epigenetic regulator. This review summarizes the role of lactylation as a central metabolic-epigenetic hub in SA-AKI pathogenesis. We detail its molecular basis, governed by a dynamic "writer-reader-eraser" network. In SA-AKI, lactylation orchestrates a multifaceted pathological cascade: it reprograms immune responses (e.g., altering macrophage polarization), disrupts tubular cell fate (e.g., inducing mitochondrial dysfunction), and compromises microvascular integrity. Its function exhibits cell-type and spatiotemporal specificity, explaining its dual roles in injury and repair. This mechanism provides a new framework for understanding SA-AKI and reveals promising translational avenues: specific lactylation marks (e.g., H3K18 lactylation) are potential diagnostic biomarkers, and targeting this axis offers novel strategies for precision therapy. Overcoming current research challenges is crucial for translating this knowledge into improved patient outcomes.

PMID:
42658356
Bibliographic data and abstract were imported from PubMed on 28 Aug 2026.

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