The Sphingolipids Metabolism Mechanism and Associated Molecular Biomarker Investigation in Keloid

Sphingolipid metabolism plays important roles in maintaining cell growth and signal transduction. However, this pathway has not been investigated in keloid, a disease characterized by the excessive proliferation of fibroblasts.Based on the expression profiles of three datasets, the differentially expressed genes (DEGs) were explored between keloid fibroblasts and normal fibroblasts. Metabolism-related genes were obtained from a previous study. Then, enrichment analysis and protein-protein interaction (PPI) network analysis were performed for genes. Differences in metabolism-related pathways between keloid fibroblasts and normal fibroblasts were analyzed by the gene set variation analysis (GSVA). Quantitative PCR was used to confirm the expression of key genes in keloid fibroblast.A total of 42 up-regulated co-DEGs and 77 down-regulated co-DEGs were revealed based on three datasets, and were involved in extracellular matrix structural constituent, collagencontaining extracellular matrix and sphingolipid metabolism pathway. A total of 15 metabolism- DEGs were screened, including serine palmitoyltransferase long chain base subunit (SPTLC) 3, UDP-glucose ceramide glucosyltransferase (UGCG) and sphingomyelin synthase 2 (SGMS2). All these three genes were enriched in the sphingolipid pathway. GSVA showed that the biosynthesis of glycosphingolipids (GSLs) in keloid fibroblasts was lower than that in normal fibroblasts. Quantitative PCR suggested SPTLC3, UGCG and SGMS2 were regulated in keloid fibroblasts.Sphingolipids metabolism pathway might take part in the disease progression of keloid by regulating keloid fibroblasts. SPTLC3, UGCG and SGMS2 might be key targets to investigate the underlying mechanism.