Lactate and lactylation: novel perspectives on fibrosis pathogenesis and therapeutic directions

Abstract Fibrosis is the common terminal pathway of abnormal tissue repair in various chronic diseases and has become a major global health challenge. Recent research has identified metabolic reprogramming as one of the key factors in the pathogenesis of fibrosis. Lactate, once considered a simple b...

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Main Authors: Huanwei Liang, Linlin Xu, Yi Yang
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-025-06748-0
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author Huanwei Liang
Linlin Xu
Yi Yang
author_facet Huanwei Liang
Linlin Xu
Yi Yang
author_sort Huanwei Liang
collection DOAJ
description Abstract Fibrosis is the common terminal pathway of abnormal tissue repair in various chronic diseases and has become a major global health challenge. Recent research has identified metabolic reprogramming as one of the key factors in the pathogenesis of fibrosis. Lactate, once considered a simple byproduct of glycolysis, has now been confirmed as a crucial metabolic messenger regulating intercellular communication and functional remodeling. The dynamic balance of intercellular lactate shuttling is essential for maintaining tissue homeostasis, and its dysregulation has been closely linked to the progression of fibrosis. Lactylation, a novel post-translational modification driven by lactate accumulation, can regulate protein function and gene expression, thereby playing a significant role in the pathogenesis of fibrosis. In this review, we summarize the latest advancements in the role of lactate and lactylation in the pathogenesis of fibrosis. By integrating the most recent research, we emphasize the importance of lactylation as a potential therapeutic target and explore the translational prospects of targeting lactate metabolism and lactylation in anti-fibrotic treatments, thereby providing novel insights for clinical intervention.
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issn 1479-5876
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publishDate 2025-07-01
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series Journal of Translational Medicine
spelling doaj-art-5bbcf8924ca6443f8cf4d58d0a9f3e882025-08-20T03:04:11ZengBMCJournal of Translational Medicine1479-58762025-07-0123111310.1186/s12967-025-06748-0Lactate and lactylation: novel perspectives on fibrosis pathogenesis and therapeutic directionsHuanwei Liang0Linlin Xu1Yi Yang2Department of Nephrology, Center for Regeneration and Aging Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang UniversitySchool of Medicine, Zhejiang UniversityDepartment of Nephrology, Center for Regeneration and Aging Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang UniversityAbstract Fibrosis is the common terminal pathway of abnormal tissue repair in various chronic diseases and has become a major global health challenge. Recent research has identified metabolic reprogramming as one of the key factors in the pathogenesis of fibrosis. Lactate, once considered a simple byproduct of glycolysis, has now been confirmed as a crucial metabolic messenger regulating intercellular communication and functional remodeling. The dynamic balance of intercellular lactate shuttling is essential for maintaining tissue homeostasis, and its dysregulation has been closely linked to the progression of fibrosis. Lactylation, a novel post-translational modification driven by lactate accumulation, can regulate protein function and gene expression, thereby playing a significant role in the pathogenesis of fibrosis. In this review, we summarize the latest advancements in the role of lactate and lactylation in the pathogenesis of fibrosis. By integrating the most recent research, we emphasize the importance of lactylation as a potential therapeutic target and explore the translational prospects of targeting lactate metabolism and lactylation in anti-fibrotic treatments, thereby providing novel insights for clinical intervention.https://doi.org/10.1186/s12967-025-06748-0LactateLactylationFibrosis
spellingShingle Huanwei Liang
Linlin Xu
Yi Yang
Lactate and lactylation: novel perspectives on fibrosis pathogenesis and therapeutic directions
Journal of Translational Medicine
Lactate
Lactylation
Fibrosis
title Lactate and lactylation: novel perspectives on fibrosis pathogenesis and therapeutic directions
title_full Lactate and lactylation: novel perspectives on fibrosis pathogenesis and therapeutic directions
title_fullStr Lactate and lactylation: novel perspectives on fibrosis pathogenesis and therapeutic directions
title_full_unstemmed Lactate and lactylation: novel perspectives on fibrosis pathogenesis and therapeutic directions
title_short Lactate and lactylation: novel perspectives on fibrosis pathogenesis and therapeutic directions
title_sort lactate and lactylation novel perspectives on fibrosis pathogenesis and therapeutic directions
topic Lactate
Lactylation
Fibrosis
url https://doi.org/10.1186/s12967-025-06748-0
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AT linlinxu lactateandlactylationnovelperspectivesonfibrosispathogenesisandtherapeuticdirections
AT yiyang lactateandlactylationnovelperspectivesonfibrosispathogenesisandtherapeuticdirections