Skin Pigmentation and Pigmentary Disorders: Focus on Epidermal/Dermal Cross-Talk

Abstract

Variation in human skin and hair color is the most notable aspect of human variability and several studies in evolution, genetics and developmental biology contributed to explain the mechanisms underlying human skin pigmentation, which is responsible for differences in skin color across the world's populations. Despite skin pigmentation is primarily related to melanocytes functionality, the surrounding keratinocytes and extracellular matrix proteins and fibroblasts in the underlying dermal compartment actively contribute to cutaneous homeostasis. Many autocrine/paracrine secreted factors and cell adhesion mechanisms involving both epidermal and dermal constituents determine constitutive skin pigmentation and, whenever deregulated, the occurrence of pigmentary disorders. In particular, an increased expression of such mediators and their specific receptors frequently lead to hyperpigmentary conditions, such as in melasma and in solar lentigo, whereas a defect in their expression/release is related to hypopigmented disorders, as seen in vitiligo. All these interactions underline the relevant role of pigmentation on human evolution and biology.

Keywords: Dermal/epidermal cross-talk; Growth factors; Melasma; Pigmentation; Solar lentigo; Vitiligo.

Fig. 1. Skin types pigmentation. In lightly pigmented skin, melanosomes are smaller, mainly at early stages I and II of maturation and they are transferred to the surrounding keratinocytes as clusters in membrane bound organelles. In darkly pigmented skin, melanosomes are more abundant, larger, at stage IV and are singly transferred to the neighbouring cells. Their degradation appears also slower than that observed in light skin, as melanins is yet detected in the stratum corneum. Immunohistochemical analysis of the expression of MART-1 in a skin specimen. Nuclei are counterstained with haematoxylin (×200).

Fig. 2. Epithelial-mesenchymal melanogenic interplay and hyperpigmentary disorders: altered expression of growth factors/mediators and their receptors regulating melanocyte functionality has been shown in several hyperpigmentations, including solar/senile lentigo, melasma, dermatofibroma and seborrhoeic keratosis (H&E, ×100). KGF: keratinocyte growth factor, KGFR: keratinocyte growth factor receptor, SCF: stem cell factor, HGF: hepatocyte growth factor, ET-1: endothelin-1, α-MSH: alpha melanocyte-stimulating hormone, ETBR: endothelin B receptor, sFRP2: secreted frizzled-related protein 2, MMP2: metalloproteinase 2, VEGF: vascular endothelial growth factor.

Fig. 3. Vitiligo as a model of deregulated epithelial-mesenchymal melanogenic interplay in hypopigmented disorders (H&E, ×100). KGF: keratinocyte growth factor, SCF: stem cell factor, ET-1: endothelin-1, GM-CSF: granulocyte macrophage colony-stimulating factor, TNF-α: tumor necrosis factor alpha, IL-1α: interleukin 1 alpha, bFGF: basic fibroblast growth factor, DKK1: dickkopf 1.