Wang_2025_J.Plast.Reconstr.Aesthet.Surg_113_592

Hypertrophic scar (HS) is a pathological outcome of wound healing, characterized by excessive fibroblast activation and abnormal extracellular matrix deposition. Recent studies indicate that metabolic changes, particularly in lipid pathways, are involved in fibroblast regulation and scar progression. Current treatments often show limited efficacy and high recurrence. To better understand the underlying mechanisms, we analyzed transcriptomic datasets of HS and normal fibroblasts. We identified 64 lipid metabolism-related genes that were differentially expressed, with enrichment in the linoleic acid and sphingolipid metabolic pathways. LASSO regression highlighted lipase A (LIPA) as a key hub gene. Receiver operating characteristic analysis confirmed the high diagnostic accuracy of LIPA. Experimental validation in TGF-beta1-stimulated fibroblasts demonstrated consistent upregulation of expression at both mRNA and protein levels. Functional assays showed that silencing LIPA significantly inhibited fibroblast proliferation and migration. Furthermore, molecular docking with five commonly used HS drugs-5-fluorouracil, betamethasone, imiquimod, triamcinolone, and verapamil-identified betamethasone as the strongest binding compound for LIPA, suggesting potential pharmacological targeting. Collectively, these findings establish LIPA as a lipid metabolism-related biomarker and therapeutic target in HS. This study provides a mechanistic framework linking lipid metabolism to scar progression and supports strategies targeting metabolic pathways for precise HS therapy.