Understanding hyperpigmentation: What factors play a role in UV-induced Long-Lasting Pigmentation (LLP)?

Human skin color, i.e. pigmentation, differs widely among individuals as do their responses to various types of ultraviolet radiation (UV) and their risks of skin cancer, including melanoma. Visual skin color is formed naturally by a dark polymeric substance known as melanin, which is produced in lysosome-related organelles within melanocytes found in the basal layer of the epidermis. The exposure of human skin to UV increases the production of melanin in the epidermis, which typically fades over time. However, in some individuals this pigmentation persists for months to years in a phenomenon termed long-lasting pigmentation (LLP). It is unclear whether LLP is an indicator of potential risk for skin cancer or provides a protective effect. LLP seems to have similar features to other forms of hyperpigmentation, e.g. solar lentigos or age spots, which are clinical markers of photodamage. To investigate what UV-induced molecular changes may persist in individuals with LLP, short-term LLP clinical specimens from non-sunburn inducing repeated UV (UVA, UVB or UVA+UVB) exposures at 4 months post-exposure were evaluated by microarray dataset mining and by immunohistochemical analysis of UV-induced melanogenic/paracrine factors. Validated targets were further evaluated in long-term LLP clinical specimens from six healthy individuals (3 LLP+ and 3 LLP-) followed greater than 9 months who initially received a single sunburn inducing UVA+UVB exposure. The UV-induced hyperpigmentation model presented suggests that basal keratinocytes have impaired melanin removal ability, which leads to a compensatory mechanism by neighboring keratinocytes with increased proliferative capacity to maintain skin homeostasis. The attenuated discovery of SOX7 and other hemidesmosomal components (integrin α6β4, plectin) leading to increased melanosome uptake points to a spatial regulation within the epidermis. The reduced density of hemidesmosomes in rete ridge areas that protrude into the dermis compared to other basement membrane epidermal areas provides supporting evidence for plasticity at the basement membrane. These results suggest that the hyperpigmentation phenomenon leading to increased rete ridge formation develops in order to maintain normal skin homeostasis in individuals with LLP.Degree awarded: Ph.D. Biology. The Catholic University of Americ