Role of lactylation-induced macrophage failed phenotypic switching in sustaining inflammation of diabetic wounds

The impaired healing of diabetic wounds is closely associated with a persistent inflammatory response, wherein macrophages, as crucial immune effector cells in the local wound microenvironment, play a vital role in maintaining inflammatory equilibrium. Increasing evidence indicates that lactate, a product of glycolysis, is now recognized as a novel regulator of macrophage function by influencing gene transcription through protein lactylation on histone and non-histone substrates. This review seeks to outline the impact of chronic inflammation on macrophage phenotype (metabolism and polarization) and to clarify how subsequent protein lactylation alters macrophage biology, thereby impacting the progression of chronic inflammatory conditions such as diabetic wounds. These findings collectively provide new insights into the pathogenesis of impaired diabetic wound healing and underscore the potential of targeting protein lactylation as a therapeutic approach against chronic inflammation.