Guanine Deaminase in Human Epidermal Keratinocytes Contributes to Skin Pigmentation.

Joon Min Jung,Young-Hoon Kim,Youngsup Song,Sung Eun Chang,Su Yeon Kim,Tai Kyung Noh,Soo Youn Jo

doi:10.3390/molecules25112637

Joon Min Jung, Young-Hoon Kim + Show 5 more

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https://doi.org/10.3390/molecules25112637

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Abstract

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.

Highlights

Skin hyperpigmentation is caused by the interplay between melanocytes and neighboring cells of keratinocytes (KCs), fibroblasts, endothelial cells, and inflammatory cells [1,2,3,4,5,6]
When generation sequencing (NGS) was performed with punch biopsy specimens of lesional and perilesional facial skin tissue obtained from three patients with Riehl’s melanosis (RM), guanine deaminase (GDA) gene expression level increased 1,283.4, 3.7, and 26.4-fold in the facial lesions of 59, 72, and 59-year-old female patients with
Among the constituent cells present in skin, KCs secrete many mitogenic or melanogenic factors recognized by corresponding receptors on melanocytes

Summary

Introduction

Skin hyperpigmentation is caused by the interplay between melanocytes and neighboring cells of keratinocytes (KCs), fibroblasts, endothelial cells, and inflammatory cells [1,2,3,4,5,6]. KCs may have the most important role as they produce abundant melanogenic mediators. KCs, the major type of skin cells, act as the first barrier to UV or environmental stress. KC production and/or growth factor and cytokine secretion are essential stress response mechanisms in response to UV irradiation, inflammatory signals, or skin injury [1,2,3]. Many paracrine factors secreted from epidermal KCs upon stimulation regulate melanogenesis. Alpha-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH) are key melanogenic stimulators secreted by human epidermal KCs upon UV irradiation [7].

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