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

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.