Histone lactylation regulates autophagy of hyperplastic scar fibroblasts by inhibiting the transcriptional activity of phosphatase and tensin homologue.

Hyperplastic scar (HS) is an overreaction of tissue to skin injury caused by local fibroblast proliferation and excessive collagen production. Histone posttranslational modification patterns are important epigenetic processes that control various biological activities. This study was designed to investigate the effects of histone lactylation on HS and the underlying mechanism. Western blot was used to analyse the lactylation level in HS patients and fibroblasts (HSFs). In vitro experiments, western blot, cell counting kit-8, and immunofluorescence staining were performed to detect the collagen level, cell viability, and autophagy, respectively. The relationship between snai2 (SLUG) and phosphatase and tensin homologue (PTEN) was assessed by RNA immunoprecipitation and dual-luciferase reporter assays. The results showed that the histone lactylation level was upregulated in HS tissues and HSFs. HSFs showed increased collagen production and cell viability, and decreased autophagy. Silencing of lactate dehydrogenase A (LDHA) promoted the transcription of PTEN by inhibiting SLUG, thus promoting autophagy. Knockdown of LDHA inhibited collagen deposition and cell viability, and increased autophagy in HSFs, and the results were reversed after PTEN inhibition. In summary, histone lactylation inhibited the transcription activity of PTEN by promoting SLUG, thereby suppressing autophagy and promoting collagen deposition and cell viability of HSFs, which might provide effective therapeutic strategies in HS.