Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation

Abstract

The high incidence, low healing rate and huge economic burden of wounds (especially chronic wounds) worldwide remain a great challenge for clinical staff and patients. The various stages of wound healing are regulated by paracrine or autocrine cytokines and growth factors, and the study of their intrinsic mechanisms is a prerequisite for better wound treatment. Lactate, the end product of glycolysis, plays a role in all stages of wound healing, and recent studies have identified lactate as an epigenetic regulator that regulates gene expression through histone lysine lactylation and stimulates posttranslational modifications to regulate related gene expression, thereby causing a series of biological functional changes. This article reviews the progress of research on lactate and lactylation during wound healing or in related diseases, including its involvement in immune regulation, inflammation control, and proliferative remodeling, and finally describes the prospects for lactate therapy regarding wound healing.

Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis

“…We speculate that TGF-β may satisfy the energy demands during HSC transdifferentiation into myofibroblasts through other metabolic pathways. Glycolysis can regulate the epigenetic mechanism of gene expression ( 50 , 51 ). Recent findings show that HK2 induces histone lactylation in HSCs ( 45 ).…”

Integrative Analysis of Lactylome and Proteome of Hypertrophic Scar To Identify Pathways or Proteins Associated with Disease Development

“…55 Additionally, lactate promotes endothelial-to-mesenchymal transition through Snail1 lactylation following myocardial infarction, 56 and both lactate and histone lactylation play a regulatory role in wound healing. 3 However, there is a scarcity of literature on the involvement of lactate and protein lactylation in hypertrophic scar formation. This study aims to investigate the protein lysine lactylation landscape in a hypertrophic scar.…”

Nanozymes for the Therapeutic Treatment of Diabetic Foot Ulcers

“…79 It also alters the pH and lactic acid deposition in the wound, thereby accelerating the formation of an unfriendly microenvironment. 80 At the same time, long unhealed wounds can be infected by multidrug resistant bacteria, which is another thorny issue. 81 Clinically, antiinfective treatment for DFU wounds is mainly based on antibiotic therapy and surgical debridement.…”

“…In addition, chronically infected wounds are infiltrated with immune cells, such as neutrophils, and unfavorable cell growth and migration, resulting in apoptosis and tissue necrosis . It also alters the pH and lactic acid deposition in the wound, thereby accelerating the formation of an unfriendly microenvironment . At the same time, long unhealed wounds can be infected by multidrug resistant bacteria, which is another thorny issue .…”