Work

Lactylation in tissue fibrosis: epigenetic mechanisms, metabolic crosstalk, and therapeutic opportunities

Year: 2026

Type: article

Abstract: BACKGROUND: Tissue fibrosis, driven by chronic inflammation and degeneration, leads to progressive organ dysfunction. While significant advancements have been made, effective therapies remain limited. Lactylation, a newly recognized post-translational modification (PTM), has attracted attention in cellular regulation. However, the precise mechanisms through which lactylation influences fibrosis remain poorly understood. MAIN BODY: In this Review, we integrate current insights into the origin, molecular mechanisms, and dynamic regulation of both histone and non-histone lactylation, with a particular focus on its mechanistic roles in tissue fibrosis. Lactylation acts as a metabolic-epigenetic interface, linking altered cellular metabolism to chromatin remodeling, transcriptional reprogramming, and activation of fibrosis-related signaling networks. Through these processes, lactylation exerts context-dependent and organ-specific effects in fibrotic diseases of the liver, kidney, lung, skin, and other tissues. Notably, its regulatory influence extends beyond non-malignant fibrotic conditions to encompass tumor-associated stromal fibrosis and fibrogenic remodeling during post-injury tissue repair. Moreover, this Review highlights the therapeutic potential of targeting both histone and non-histone lactylation in fibrosis and explores its crosstalk with other PTMs, including acetylation and methylation. CONCLUSION: Lactylation represents a critical metabolic-epigenetic axis in the initiation and progression of tissue fibrosis. Targeting lactylation-either by modulating specific lactylation sites or regulating lactatemetabolizing key enzymes-offers an effective approach to suppress fibrosis progression and provides a foundation for the development of precision antifibrotic therapies.

Source: Journal of Translational Medicine

DOI: 10.1186/s12967-026-08046-9

Authors: Zhe Qiu, Yifan Zhang, Xiaoyan Li, Zhibo Xie

Institutions: Shanghai Jiao Tong University, Shanghai Children's Hospital, Shanghai Ninth People's Hospital

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,890