Abstract
Background
Actinic lentigos (AL) are benign hyperpigmented skin lesions associated with photoageing. Despite their high prevalence, biological mechanisms driving their formation remain unclear.
Objectives
To provide new insights about the physiopathology of AL through a comprehensive description of their histological and molecular features.
Methods
Quantitative analysis of dermoscopic images was used to select AL containing elongated patterns, predicted to display a highly deformed dermal-epidermal junction (DEJ), on the back of hands of 15 Caucasian women. Biopsies from lesional and adjacent non-lesional (NL) areas were processed for histological analysis or gene expression profiling.
Results
Histological staining confirmed a drastic deformation of the DEJ in AL, with deep epidermal invaginations into the dermis. Although the melanin content was significantly higher in AL compared to NL epidermis, the distribution of melanocytes along the DEJ was unchanged.
Transcriptomic analysis revealed a signature of 529 genes differently expressed in AL versus NL skin. Alteration of epidermal homeostasis was confirmed by the dysregulation of keratinocyte proliferation and differentiation markers. Surprisingly, canonical genes involved in melanogenesis were not significantly modulated in AL. A striking finding was the overexpression of a large group of genes involved in dermal extracellular matrix organization and remodelling. Dermal alterations were confirmed by immunolabellings on AL and NL sections.
Conclusions
Drastic disorganization of the cutaneous structure in AL is accompanied by a specific molecular signature revealing alterations in both epidermal and dermal compartments. Particularly, our results suggest that local modifications of the dermal extracellular matrix might contribute to hyperpigmentation in AL.
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