Dyspigmented hypertrophic scars: Beyond skin color

Abstract

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.

Galectin‐1 production is elevated in hypertrophic scar

“…Within this list of DEGs were mostly genes involved in ECM synthesis and remodeling such as collagens and metalloproteinases, including several galectins—fold changes of differentially expressed galectin and collagen genes are listed in Table 2. The full lists of DEGs identified have been previously published elsewhere 21,24,25 . Transcription of LGALS1, 4, and 12 were significantly differentially regulated between porcine NS and HTS (FDR <0.01); LGALS1 mRNA was consistently overexpressed in scar tissues (Table 2).…”

Outcome of Repeated Use of Donor Site for Noncultured Epidermal Cellular Grafting in Stable Vitiligo: A Retrospective Study

“…However, the difference was the amount of melanin and α -melanocyte-stimulating hormone ( α -MSH) in the lesion [11]. Another study conducted by Alkhalil et al also demonstrated a difference in cellular activities and gene transcription in hypopigmented and hyperpigmented scars, without differences in the number of melanocytes [12]. In addition, keratinocytes and fibroblasts can be stimulated to produce various cytokines that regulate melanocyte survival, proliferation, migration, and differentiation [13, 14].…”

Hypopigmented burn hypertrophic scar contains melanocytes that can be signaled to re-pigment by synthetic alpha-melanocyte stimulating hormone in vitro

“…Hyper- and hypo-pigmented epidermal sheets were stained with a melanocyte marker, S100β by an en face staining technique adapted from a previously described method [ 23 ]. The protocol used a primary S100β antibody diluted in 3% milk (1:50; ab11178) (Abcam, Cambridge, MA) and a secondary antibody (anti-mouse-CY3 at 1:100; Abcam) with subsequent DAPI application [ 24 ]. During the course of the study, the production of one S100β antibody was discontinued by the company, and the antibody was replaced with a new one (1:100; ab52642), and stains were completed with anti-rabbit-CY3 secondary antibodies.…”