Comprehensive analysis of melanogenesis and proliferation potential of melanocyte lineage in solar lentigines

Yamada, Takaaki; Hasegawa, Seiji; Inoue, Yu; Date, Yasushi; Arima, Masaru; Yagami, Akiko; Iwata, Y.; Abe, Mihoko; Takahashi, Masuhiro; Yamamoto, Naoki; Mizutani, Hiroshi; Nakata, Satoshi; Matsunaga, Kayoko; Akamatsu, Hirohiko

doi:10.1016/j.jdermsci.2013.11.005

Cited by 28 publications

(31 citation statements)

References 26 publications

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“…Our results are in agreement with data from Unver et al . but in contradiction to two studies reporting an increased number of melanocytes per length of DEJ . To support our findings, no sign of melanocyte proliferation, nor the presence of foci of melanocytes were observed.…”

Section: Discussionsupporting

confidence: 77%

“…This is supported by molecular data showing that levels of melanocyte‐ or melanogenesis‐related genes are not significantly altered in lesional skin compared with adjacent NL skin. This is a particularly striking result as most previous studies have reported an upregulation of genes or proteins involved in melanin synthesis, melanosome biogenesis or melanogenesis regulation in AL . Overall, our results suggest normal melanocyte homeostasis within the lesions selected for this study.…”

Section: Discussionsupporting

confidence: 75%

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Morphological and molecular characterization of actinic lentigos reveals alterations of the dermal extracellular matrix

et al. 2017

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Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 75%

Morphological and molecular characterization of actinic lentigos reveals alterations of the dermal extracellular matrix

et al. 2017

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“…The regulation of genes associated with the WNT signalling pathways has been described in age spots as well as melasma. Increased sFRP‐1 and FRZB/sFRP3 together with increased WNT1, WNT5a and Frizzled‐4 expression were found in age spots , whereas increased WNT expression increases in WIF1, sFRP2 and WNT5a were observed in melasma . We observed decreased levels of sFRP‐1 and DKK1 indicating that changes in at least the former of these fibroblast proteins induced by HSA have the potential to reduce melanogenesis and age spot expression.…”

Section: Discussionmentioning

confidence: 62%

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

Schütz

Rawlings²,

Wandeler

et al. 2019

Intern J of Cosmetic Sci

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IntroductionWe report on the preparation and efficacy of 10‐hydroxystearic acid (HSA) that improves facial age spots and conspicuous pores.MethodsThe hydration of oleic acid into HSA was catalyzed by the oleate hydratase from Escherichia coli. Following treatment with HSA, collagen type I and type III was assessed in primary human dermal fibroblasts together with collagen type III, p53 protein levels and sunburn cells (SBC) after UVB irradiation (1 J cm−2) by immunohistochemistry on human ex vivo skin. UVB‐induced expression of matrix metalloprotease‐1 (MMP‐1) was determined from full thickness skin by RT‐qPCR. Modification of the fibroblast secretome by HSA was studied by mass‐spectrometry‐based proteomics. In a full‐face, double blind, vehicle‐controlled trial HSA was assessed for its effects on conspicuous facial pore size and degree of pigmentation of age spots in Caucasian women over an 8‐week period.ResultsHSA was obtained in enantiomeric pure, high yield (≥80%). Collagen type I and type III levels were dose‐dependently increased (96% and 244%; P < 0.01) in vitro and collagen type III in ex vivo skin by +57% (P < 0.01) by HSA. HSA also inhibited UVB‐induced MMP‐1 gene expression (83%; P < 0.01) and mitigated SBC induction (−34% vs. vehicle control) and reduced significantly UV‐induced p53 up‐regulation (−46% vs. vehicle control; P < 0.01) in irradiated skin. HSA modified the fibroblast secretome with significant increases in proteins associated with the WNT pathway that could reduce melanogenesis and proteins that could modify dermal fibroblast activity and keratinocyte differentiation to account for the alleviation of conspicuous pores. Docking studies in silico and EC50 determination in reporter gene assays (EC50 5.5 × 10−6 M) identified HSA as a peroxisomal proliferator activated receptor‐α (PPARα) agonist. Clinically, HSA showed a statistically significant decrease of surface and volume of skin pores (P < 0.05) after 8 weeks of application and age spots became significantly less pigmented than the surrounding skin (contrast, P < 0.05) after 4 weeks.ConclusionHSA acts as a PPARα agonist to reduce the signs of age spots and conspicuous pores by significantly modulating the expression of p53, SBC, MMP‐1 and collagen together with major changes in secreted proteins that modify keratinocyte, melanocyte and fibroblast cell behavior.

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“…Hyperpigmentation in SLs is caused by the enhancement of both melanogenesis and melanocytogenesis . Differentiation of McSCs in the bulge region of hair follicles is thought to be promoted by excessive WNT1 expression in the epidermal keratinocytes, which probably increases the number of melanocytes .…”

Section: Discussionmentioning

confidence: 99%

“…Solar lentigines (SLs), hyperpigmented maculae, appear on the sun‐exposed skin of middle‐aged and older people, and are considered results of cumulative UV exposure . Pathological analysis of SL lesions revealed significant increases in melanin content and the number of melanocytes . Previous studies demonstrated that endothelin‐1 (ET‐1), stem cell factor (SCF) and other major melanogenesis‐stimulating factors were highly expressed in the lesions .…”

Section: Introductionmentioning

confidence: 99%

UV irradiation‐induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines

Yamada

Hasegawa

Iwata

et al. 2019

Experimental Dermatology

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Wnt/β‐catenin signalling promotes melanogenesis in melanocytes and also induces melanocytogenesis from melanocyte stem cells (McSCs). Previous study reported that WNT1, a ligand which activates Wnt/β‐catenin signalling pathway, was more highly expressed in the epidermis at SLs than in normal skin areas, suggesting that WNT1 causes hyperpigmentation. To elucidate the mechanism by which WNT1 expression is increased in SLs, we examined the methylation of 5‐carbon of cytosine (5mC), that is 5‐methylcytosine (5mC) level, in a region within the WNT1 promoter; the methylation of the region was known to negatively regulate WNT1 gene expression. We used an immortalized cell line of human interfollicular epidermal stem cells to analyse the effect of UVB irradiation on DNA methylation level of WNT1 promoter and found that UVB irradiation caused demethylation of WNT1 promoter and promoted WNT1 mRNA expression. It was also found that UVB irradiation reduced the expression of DNA methyltransferase 1 (DNMT1), an enzyme responsible for maintaining methylation patterns during cell division. Pathological analysis of SLs and non‐SL regions in the human skin revealed that both DNMT1 expression and 5mC level were decreased at SLs compared to non‐SL skins. Furthermore, bisulphite sequencing showed that the methylated CpG level in WNT1 promoter was also lower at SLs than in non‐SL skins. Thus, in the skin exposed to a high amount of UV rays, excessive expression of WNT1 is thought to be caused by the demethylation of WNT1 promoter, and the upregulated WNT1 promotes melanocytogenesis and melanogenesis, then resulting in SL formation.

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Comprehensive analysis of melanogenesis and proliferation potential of melanocyte lineage in solar lentigines

Cited by 28 publications

References 26 publications

Morphological and molecular characterization of actinic lentigos reveals alterations of the dermal extracellular matrix

Morphological and molecular characterization of actinic lentigos reveals alterations of the dermal extracellular matrix

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

UV irradiation‐induced DNA hypomethylation around WNT1 gene: Implications for solar lentigines

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