BioProject

Although pigment synthesis is well understood, relevant mechanisms of psychologically debilitating dyspigmentation in nascent tissue after cutaneous injuries are still unknown. More...

Although pigment synthesis is well understood, relevant mechanisms of psychologically debilitating dyspigmentation in nascent tissue after cutaneous injuries are still unknown. Here, differences in genomic transcription of hyper- and hypopigmented tissue relative to uninjured skin were investigated using a red Duroc swine scar model. Transcription profiles differed based on pigmentation phenotypes with a trend of more upregulation or downregulation in hyper- or hypopigmented scars, respectively. Ingenuity Pathway Analysis of significantly modulated genes in both pigmentation phenotypes showed pathways related to redox, metabolic, and inflammatory responses were more present in hypopigmented samples, while those related to stem cell development differentiation were found mainly in hyperpigmented samples. Cell-cell and cell-extracellular matrix interactions and inflammation responses were predicted (z-score) active in hyperpigmented and inactive in hypopigmented. The proinflammatory high-mobility group box 1 pathway showed the opposite trend. Analysis of differentially regulated mutually exclusive genes showed an extensive presence of metabolic, proinflammatory, and oxidative stress pathways in hypopigmented scars, while melanin synthesis, glycosaminoglycans biosynthesis, and cell differentiation pathways were predominant in hyperpigmented scar. Several potential therapeutic gene targets have been identified. Overall design: The red Duroc swine wound model was selected because of many similarities its skin shares with that of human, which made this animal models the prime choice for human wound healing and burn studies. Juvenile castrated male Duroc swine were used to minimize potential interference from the estrogen cycle and to reduce animal aggressiveness. A total of 28 biopsies were collected from two red Duroc pigs, and the transcriptome changes in these biopsies were evaluated during the course of wound healing and scar formation in the context of dyspigmentation. Less...