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Keloids are disfiguring fibroproliferative lesions that can occur in susceptible individuals following any skin injury. They are extremely challenging to treat, with relatively low response rates to current therapies and high rates of recurrence after treatment. Although several distinct genetic loci have been associated with keloid formation in different populations, there has been no single causative gene yet identified and the molecular mechanisms guiding keloid development are incompletely understood. Further, although it is well known that keloids are more commonly observed in populations with dark skin pigmentation, the basis for increased keloid risk in skin of colour is not yet known. Because individuals with dark skin pigmentation are at higher risk for vitamin D deficiency, the role of vitamin D in keloid pathology has gained interest in the keloid research community. A limited number of studies have found lower serum vitamin D levels in patients with keloids, and reduced expression of the vitamin D receptor (VDR) in keloid lesions compared with uninjured skin. Vitamin D has documented anti‐inflammatory, anti‐proliferative and pro‐differentiation activities, suggesting it may have a therapeutic role in suppression of keloid fibrosis. Here we review the evidence supporting a role for vitamin D and VDR in keloid pathology. [ABSTRACT FROM AUTHOR]

Keloids are fibroproliferative lesions resulting from an abnormal wound healing process due to pathological mechanisms that remain incompletely understood. Keloids tend to occur more frequently in anterior versus posterior body regions (e.g., ears, face, upper torso); this has been attributed to higher skin tension in those areas, although this has not yet been conclusively proven. Previous studies reported reduced expression of multiple homeobox (HOX) genes in keloid versus normal fibroblasts, suggesting a role for HOX genes in keloid pathology. However, HOX genes are differentially expressed along the anterior–posterior axis. Hypothetically, differential HOX expression may be due to differences in body sites, as matched donor sites are often unavailable for keloids and normal skin. To better understand the basis for differential HOX gene expression in cells from keloids compared with normal skin, we compared HOXA7, HOXA9, HOXC8 and HOXC11 expression in keloid and normal skin‐derived fibroblasts from various body sites. When keloid (N = 20) and normal (N = 12) fibroblast cell strains were evaluated, expression of HOXA7, HOXA9 and HOXC8 was significantly lower in keloid versus normal fibroblasts. However, HOX gene expression was lower in fibroblasts from more anterior versus posterior body sites. When keloid and normal cells from similar body sites were compared, differential HOX expression was not observed. To investigate the phenotypic relevance of HOX expression, HOXA9 was overexpressed in keloid and normal fibroblasts. HOXA9 overexpression did not affect proliferation but significantly reduced fibroblast migration and altered gene expression. The results suggest that differential HOX expression may be due to differences in positional identity between keloid and normal fibroblasts. However, HOX genes can potentially regulate fibroblast phenotype, suggesting that differential HOX gene expression may play a role in keloid development in anterior body sites. [ABSTRACT FROM AUTHOR]

Keloids are disfiguring scars that extend beyond the original wound borders and resist treatment. Keloids exhibit excessive extracellular matrix deposition, although the underlying mechanisms remain unclear. To better understand the molecular basis of keloid scarring, here we define the genomic profiles of keloid fibroblasts and keratinocytes. In both cell types, keloid-derived cells exhibit differential expression of genes encompassing a diverse set of functional categories. Strikingly, keloid keratinocytes exhibited decreased expression of a set of transcription factor, cell adhesion, and intermediate filament genes essential for normal epidermal morphology. Conversely, they exhibit elevated expression of genes associated with wound healing, cellular motility, and vascular development. A substantial number of genes involved in epithelial-mesenchymal transition were also up-regulated in keloid keratinocytes, implicating this process in keloid pathology. Furthermore, keloid keratinocytes displayed significantly higher migration rates than normal keratinocytes in vitro and reduced expression of desmosomal proteins in vivo. Previous studies suggested that keratinocytes contribute to keloid scarring by regulating extracellular matrix production in fibroblasts. Our current results show fundamental abnormalities in keloid keratinocytes, suggesting they have a profoundly more direct role in keloid scarring than previously appreciated. Therefore, development of novel therapies should target both fibroblast and keratinocyte populations for increased efficacy. [ABSTRACT FROM AUTHOR]