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. 2023 Oct 12:16:2847-2853.
doi: 10.2147/CCID.S402168. eCollection 2023.

Expression of Endothelin-1, Endothelin Receptor-A, and Endothelin Receptor-B in facial melasma compared to adjacent skin

Carolina Nunhez da Silva  1 , Hélio Amante Miot  1 , Tony Fernando Grassi  2 , Luciane Alarcão Dias-Melício  2   3   4 , Leandro Santos  2   3 , Ana Cláudia Cavalcante Espósito  1
Affiliations

Expression of Endothelin-1, Endothelin Receptor-A, and Endothelin Receptor-B in facial melasma compared to adjacent skin

Carolina Nunhez da Silva et al. Clin Cosmet Investig Dermatol. .

Abstract

Background/objectives: Although melasma is highly prevalent, its pathogenesis is not yet fully understood. In the skin, endothelin-1 (ET-1) is primarily produced by keratinocytes in response to UVB exposure, which is mediated by an increase in IL-1α or reactive oxygen species. ET-1 plays a role in melanogenesis by binding to specific receptor B (ERB) or receptor A (ERA). However, the expression of ET-1, ERA, and ERB in melasma has not been systematically investigated. The objective of this study was to evaluate the expression of ET-1, ERA, and ERB in facial melasma compared to the adjacent unaffected skin.

Methods: Cross-sectional study, with 40 skin samples (20: facial melasma; 20: adjacent unaffected skin) from women with facial melasma without treatment for 30 days except for sunscreen. A triple staining immunofluorescence technique was performed for anti-vimentin, DAPI, plus one of the following antibodies: (a) anti-ET1, (b) anti-ERA; (c) anti-ERB. Interfollicular areas on the slides of each topography (melasma; unaffected skin) were photographed in triplicate under confocal laser microscopy. The mean staining intensities of the image histograms (0-255 pixels intensity) were estimated for different types of cells (suprabasal keratinocytes, basal layer, and upper dermis) and were blindly compared between topographies.

Results: The mean (SD) age of the participants was 44.9 (9.2). The expression of ET-1 was increased in the whole epidermis with melasma when compared to the adjacent skin, being 32.8% (CI95% 14.7%-52.6%) higher in the spinous layer (p=0.013), 30.4% (CI95% 13.7%-47.9%) higher in the basal layer (p=0.014), and 29.7% (CI95% 11.4%-49.7%) higher in the melanocytes (p=0.006). There was no noticeable expression of ET-1 within the cells on the upper dermis. Neither ERA nor ERB resulted in differential epidermal expression between melasma and unaffected skin (p≥0.1).

Conclusion: ET-1 is expressed more intensely on the epidermis from the skin with facial melasma compared to the unaffected adjacent skin.

Keywords: endothelin receptor-A; endothelin receptor-B; endothelin-1; immunofluorescence technique; melasma.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Relative fluorescence (ET-1, ERA, and ERB) in the cytoplasm of cells from the epidermis in facial melasma and in the adjacent photoexposed nonlesional skin (n = 20 women). *p<0.05.
Figure 2
Figure 2
Overlapping direct immunofluorescence images in melasma: cytoplasmic labeling of melanocytes and keratinocytes (×100). Anti-endothelin-1—green; vimentin—red; 4’, 6-diamidino-2-phenylindole—blue.
See this image and copyright information in PMC

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Grants and funding

FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) – grant 2021/08361-9.