Transcriptome analysis of differentially expressed genes between keloid and normal skin samples reveals mitochondrial dysfunction and metabolism disruption

Background: Keloids are pathological scar that can be pruritic, painful and disfiguring. Genetic predisposition for keloids exists, and little is known about keloid patients in Zunyi, China and the molecular changes associated with keloid formation. Methods:The present study used whole-genome RNA-Seq to analyze aberrant gene expression patterns between 17 keloids and 8 normal skin samples collected at Affiliated Hospital of Zunyi Medical University, followed by comprehensive bioinformatic analysis. Results: Principal component analysis showed distinct gene expression patterns between keloids and normal skins. Using the criteria of FDR <0.01, there were 2610 differentially expressed genes (DEGs), and selected DEGs were verified via qPCR. Ingenuity pathway analysis (IPA), Gene Oncology, and KEGG analysis showed that Oxidative phosphorylation, Mitochondria 3612dysfunction, Sirtuin signaling pathway and Metabolism downregulations were mostly affected canonical pathways. The TP53, tumor microenvironment TLE3, mitochondrial protein UQCC3 and ClpP were top upstream regulators. TGF-β1 is the key molecule for keloid formation and progression. Down-regulation of metabolism-related molecules such as CPT1B, Insulin, INSR and PPARGC1A suggests metabolic dysfunction, along with endocrine disruption. Conclusions: This transcriptome profiling of keloids revealed multiple molecular mechanisms associated with keloid development and progression, which could add our understanding of molecular events of keloids formation to develop treatment strategies.