Proteínas associadas à melanogênese: análise na mucosa oral e influência da exposição solar nos nevos melanocíticos bucais

Abstract

Melanocytes play a crucial role in protecting against ultraviolet (UV) radiation through melanin production. However, their functions and distribution in sun-protected tissues, such as the oral mucosa, remain poorly understood. TRP2 and MiTF proteins are essential regulators of melanogenesis, and genetic alterations or disruptions in this process can lead to melanocytic lesions, such as nevi. While acquired melanocytic nevi are common in the skin, their occurrence in the oral mucosa is rare, and the impact of UVB exposure on the development of vermilion lip nevi remains unclear. This study aimed to investigate melanocyte function in photoprotected regions and evaluate key melanogenesis proteins in the oral mucosa and oral nevi (intraoral vs. vermilion lip), considering exposure to solar radiation. The research was conducted in three phases: 1) a cross-sectional study of the oral mucosa, 2) a literature review on melanocytes in photoprotected regions, and 3) a cross-sectional study of oral nevi. In the first phase, 30 oral mucosa samples from six subsites were analyzed using Fontana-Masson staining, immunohistochemistry, and RT-qPCR for TRP2 and MiTF. In phase 2, a narrative review was conducted using PubMed. In phase 3, 34 samples of melanocytic nevi (14 intraoral and 20 from the vermilion of the lip) were characterized histologically, with additional immunohistochemistry and RT-qPCR for TRP2 and MiTF. Results from the first phase showed that 30.0% of the samples were positive for Fontana-Masson staining, with the hard palate, buccal mucosa, and floor of the mouth showing the highest frequency. TRP2 and MiTF were immunopositive in 63.3% of the samples, particularly in the buccal mucosa, gingiva, hard palate, and floor of the mouth. RT-qPCR revealed low expression of TRP2 and MiTF, though TRP2 mRNA expression was significantly higher in the gingiva compared to the tongue (p<0.05). The literature review indicated that melanocytes are present in several human tissues not exposed to solar radiation, such as the heart, adipose tissue, and mucous membranes. These cells perform roles beyond melanogenesis, including neuroendocrine, immunoinflammatory, and antioxidant activities. In the third phase, histological analysis showed that intraoral nevi displayed asymmetry and lacked thecae, floret cells, mitoses, or pleomorphism, while vermilion nevi exhibited symmetry, formation of thecae, floret cells, pleomorphism, and solar elastosis. Protein and mRNA expression of TRP2 and MiTF was increased in both groups (p<0.05) relative to the oral mucosa, though no significant differences were observed between them (p>0.05). In conclusion, melanocytes are present in different examined sites of the oral mucosa, with a higher prevalence in the buccal mucosa, gingiva, and hard palate. Similar to other sun-protected regions, these cells likely play roles beyond melanin production, as evidenced by the diverse functions described in the literature. This is consistent with the low expression of TRP2 and MiTF mRNA in the oral mucosa observed in this study. Although intraoral and vermilion nevi show distinct histopathological features, their similar expression of TRP2 and MiTF suggests that factors other than UVB exposure may influence the development of these lesions.