Figure 2.

Melanocyte activation integrated in the schematic view of the UV-induced pigmentation pathway in the normal skin. Once stimulated by UV light, p53 initiates the release by keratinocyte of melanogenic paracrine growth factors and cytokines: adrenocorticotropic hormone (ACTH),⁵² α-melanocyte-stimulating hormone (α-MSH),^52,53 endothelin-1 (ET-1),^54–56 stem cell factor (SCF),⁵⁷ hepatocyte growth factor (HGF),⁵⁸ basic fibroblast growth factor (bFGF),^54,56 leukemia inhibitory factor (LIF),⁵⁹ and granulocyte macrophage colony-stimulating factor (GM-CSF).^60,61 The keratinocyte factors further interact with their corresponding receptors on melanocytes, and induce melanocyte activation, with subsequent stimulation of microphtalmia-associated transcription factor (MITF)^62,63 and its downstream targets, the melanogenic enzymes Tyrosinase (TYR), Tyrosinase-related protein 1 (TYRP1), and Dopachrome tautomerase (DCT); this cascade leads to synthesis of melanin and melanocyte differentiation (see Fig. 4). MITF, the master regulator of melanogenic pathway, is activated through three signaling pathways regulated by cAMP,^64,65 protein kinase C (PKC),^63,66,67 and mitogen-activated protein kinase (MAPK)^63,67 to subsequently induce proliferation and differentiation of human melanocytes.⁶⁸ Figure based and modified from [62, 63]. UVB was shown to induce all keratinocyte factors included in the figure. *Factors activated by both UVB and UVA. Figure 2 was done by the medical illustrator Debbie Maizels.