Guanine Deaminase in Human Epidermal Keratinocytes Contributes to Skin Pigmentation

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 11; p. 2637
• Main Authors: Jung, Joon Min, Noh, Tai Kyung, Jo, Soo Youn, Kim, Su Yeon, Song, Youngsup, Kim, Young-Hoon, Chang, Sung Eun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.06.2020; MDPI
• Subjects: Adenoviruses; Adult; Aged; Case-Control Studies; Cell culture; Cells, Cultured; Coculture Techniques; Culture Media, Conditioned; Cytokines; DNA microarrays; Endothelin 1; Endothelin-1 - metabolism; Enzymes; Epidermis; Female; Fibroblasts; Gene expression; Growth factors; Guanine; Guanine deaminase; Guanine Deaminase - genetics; Guanine Deaminase - metabolism; Humans; Hyperpigmentation; Hyperpigmentation - enzymology; Hyperpigmentation - pathology; Immunofluorescence; Inflammation; Irradiation; Keratinocytes; Keratinocytes - metabolism; Kinases; Lesions; Melanin; Melanins - metabolism; Melanocytes; Melanocytes - enzymology; Melanocytes - pathology; melanogenesis; Melanosis; Metabolism; Metabolites; Middle Aged; Pigmentation; Senescence; siRNA; Skin; Skin Pigmentation; Stem cell factor; Stem Cell Factor - metabolism; Stem cells; Studies; Tumor necrosis factor-TNF; Ultraviolet radiation; UV radiation; UV radiation; melanogenesis; guanine deaminase
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25112637

Epidermal keratinocytes are considered as the most important neighboring cells that modify melanogenesis. Our previous study used microarray to show that guanine deaminase (GDA) gene expression is highly increased in melasma lesions. Hence, we investigated the role of GDA in skin pigmentation. We examined GDA expression in post-inflammatory hyperpigmentation (PIH) lesions, diagnosed as Riehl's melanosis. We further investigated the possible role of keratinocyte-derived GDA in melanogenesis by quantitative PCR, immunofluorescence staining, small interfering RNA-based GDA knockdown, and adenovirus-mediated GDA overexpression. We found higher GDA positivity in the hyperpigmentary lesional epidermis than in the perilesional epidermis. Both UVB irradiation and stem cell factor (SCF) plus endothelin-1 (ET-1) were used, which are well-known melanogenic stimuli upregulating GDA expression in both keratinocyte culture alone and keratinocyte and melanocyte coculture. GDA knockdown downregulated melanin content, while GDA overexpression promoted melanogenesis in the coculture. When melanocytes were treated with UVB-exposed keratinocyte-conditioned media, the melanin content was increased. Also, GDA knockdown lowered SCF and ET-1 expression levels in keratinocytes. GDA in epidermal keratinocytes may promote melanogenesis by upregulating SCF and ET-1, suggesting its role in skin hyperpigmentary disorders.