scholarly journals Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release

2021 ◽  
Vol 22 (22) ◽  
pp. 12501
Author(s):  
Kyung Ah Cheong ◽  
In Sup Kil ◽  
Hyuk Wan Ko ◽  
Ai-Young Lee
Keyword(s):  
Uric Acid ◽  
The Elderly ◽  
Epidermal Keratinocytes ◽  
Seborrheic Keratosis ◽  
Human Epidermal Keratinocytes ◽  
Skin Hyperpigmentation ◽  
Guanine Deaminase ◽  
Acid Release ◽  
Skin Specimen

Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (GDA) has been identified to cause UV-induced keratinocyte senescence in seborrheic keratosis. Seborrheic keratosis is also frequently pigmented. Growing evidences indicate that hyperuricemia is a risk factor of acanthosis nigricans, an acquired skin hyperpigmentation. The objective of this study was to investigate role of GDA and its metabolic end product, uric acid, in hyperpigmentation of patients with seborrheic keratosis using their lesional and non-lesional skin specimen sets and cultured primary human epidermal keratinocytes with or without GDA overexpression or uric acid treatment. GDA-overexpressing keratinocytes or their conditioned media containing uric acid increased expression levels of MITF and tyrosinase in melanocytes. Uric acid released from keratinocytes was facilitated by ABCG2 transporter with the help of PDZK1 interaction. Released uric acid was taken by URAT1 transporter in melanocytes, stimulating melanogenesis through p38 MAPK activation. Overall, GDA upregulation in seborrheic keratosis plays a role in melanogenesis via its metabolic end product uric acid, suggesting that seborrheic keratosis as an example of hyperpigmentation associated with photoaging.

scholarly journals Guanine Deaminase in Human Epidermal Keratinocytes Contributes to Skin Pigmentation

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2637
Author(s):  
Joon Min Jung ◽  
Tai Kyung Noh ◽  
Soo Youn Jo ◽  
Su Yeon Kim ◽  
Youngsup Song ◽  
...  
Keyword(s):  
Stem Cell Factor ◽  
Small Interfering Rna ◽  
Skin Pigmentation ◽  
Epidermal Keratinocytes ◽  
Melanin Content ◽  
Human Epidermal Keratinocytes ◽  
Guanine Deaminase ◽  
Keratinocyte Culture ◽  
Interfering Rna

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.

scholarly journals Expression and functional role of Sox9 in human epidermal keratinocytes

2013 ◽  
Vol 69 (2) ◽  
pp. e42
Author(s):  
Jeung-Hoon Lee ◽  
Ge Shi ◽  
Kyung-Cheol Sohn ◽  
Zhengjun Li ◽  
Dae-Kyoung Choi ◽  
...  
Keyword(s):  
Functional Role ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

scholarly journals U‐Shaped Association Between Serum Uric Acid Levels With Cardiovascular and All‐Cause Mortality in the Elderly: The Role of Malnourishment

2018 ◽  
Vol 7 (4) ◽  
Author(s):  
Wei‐Cheng Tseng ◽  
Yung‐Tai Chen ◽  
Shuo‐Ming Ou ◽  
Chia‐Jen Shih ◽  
Der‐Cherng Tarng ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
The Elderly ◽  
All Cause Mortality

scholarly journals Expression and Functional Role of Sox9 in Human Epidermal Keratinocytes

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e54355 ◽  
Author(s):  
Ge Shi ◽  
Kyung-Cheol Sohn ◽  
Zhengjun Li ◽  
Dae-Kyoung Choi ◽  
Young Min Park ◽  
...  
Keyword(s):  
Functional Role ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

scholarly journals Role of keratin 24 in human epidermal keratinocytes

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0174626 ◽  
Author(s):  
Min Min ◽  
Xi-Bei Chen ◽  
Ping Wang ◽  
Lilla Landeck ◽  
Jia-Qi Chen ◽  
...  
Keyword(s):  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

scholarly journals Corticotropin-releasing hormone stimulates NF-kappaB in human epidermal keratinocytes

2004 ◽  
Vol 181 (3) ◽  
pp. R1-R7 ◽  
Author(s):  
B Zbytek ◽  
LM Pfeffer ◽  
AT Slominski
Keyword(s):  
Nuclear Factor Kappa B ◽  
Primary Cultures ◽  
Human Keratinocytes ◽  
Epidermal Keratinocytes ◽  
Corticotropin Releasing Hormone ◽  
Human Epidermal Keratinocytes ◽  
Releasing Hormone ◽  
Epidermal Homeostasis ◽  
Nf Kappab

Corticotropin-releasing hormone (CRH) has been shown to inhibit proliferation and modulate expression of inflammation markers in the epidermal cells. In the present study we report that CRH also stimulates nuclear factor-kappa B (NF-kappaB) activity. Incubation with CRH of human keratinocytes derived from primary cultures resulted in increased binding of DNA by NF-kappaB. CRH induced translocation of NF-kappaB subunit p65 from the cytoplasm to the nucleus and induced expression of kappaB-driven chloramphenicol acetyltransferase (CAT) reporter gene. NF-kappaB translocation was accompanied by degradation of the inhibitor of NF-kappaB alpha (IkappaB-alpha). Specificity of the CRH effect was demonstrated by the use of CRH-R antagonists antalarmin and alpha-helical CRH [9-41]. CRH-dependent stimulation of NF-kappaB activity is consistent with accumulated data about role of this neuropeptide in the regulation of local epidermal homeostasis.

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