The researchers found elevated lactate levels and increased expression of the lactate transporter MCT1 within hypertrophic scar tissue. Macrophages exposed to stiff mechanical environments were identified as the primary source of lactate production. 

According to the study, lactate uptake by dermal fibroblasts triggered histone H3 lysine 23 lactylation (H3K23la), an epigenetic modification that promoted activation of pro-fibrotic genes linked to collagen deposition and scar progression. 

The authors also identified a self-reinforcing feedback loop involving the genes HEY2 and COL11A1, which appeared to amplify fibrosis and fibroblast hyperactivation within scar tissue. 

Importantly, fibroblast-specific deletion or pharmacological inhibition of MCT1 in mouse models reduced collagen deposition, accelerated wound healing and attenuated hypertrophic scar formation. 

The findings contribute to growing understanding of how metabolic signalling, immune-cell activity and epigenetic regulation interact during pathological wound healing. The authors suggest the MCT1-H3K23la pathway may represent a future therapeutic target for hypertrophic scarring and fibrosis-related skin disorders.