An explanation for the mysterious distribution of melanin in human skin: a rare example of asymmetric (melanin) organelle distribution during mitosis of basal layer progenitor keratinocytes

Joly‐Tonetti, Nicolas; Wibawa, Judata I.; Bell, Mike; Tobin, Desmond J.

doi:10.1111/bjd.16926

Cited by 25 publications

(36 citation statements)

References 34 publications

(41 reference statements)

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“…Namely, after being transferred to keratinocytes through exo-/endocytosis of the melanosome core (melanocore) 69 , melanin's concentration is regulated via the asymmetric distribution of melanin between daughter keratinocytes (the one remains in the basal layer and 'inheriting' most of the melanin, while the other destines to differentiate and stratify, and inherits a much smaller fraction of 'maternal' melanin) 11 and, possibly, other mechanisms. In general, we can conclude that the degradation of melanin does not occur completely and it can be found in the upper layers of the epidermis, even in the superficial areas of the stratum corneum, and novel molecular-specific methods are required for studying the fate of melanin in the skin.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to this, Raman microspectroscopy-based approach relies on the crosscheck of the signal origin by simultaneously analyzing the fluorescence and Raman spectra in each point. Hence, the first task where this approach can find application is the investigation of melanin fate and its redistribution in the epidermis upon stress conditions such as UV exposure 2 , 68 , oxidative and mechanical stress 11 , etc. Although this task is seemingly simple, the fact is that a number of questions about the melanin fate (such as the presence of “melanin dust” in the stratum corneum 13 , 14 ), kinetics and mechanisms of its transfer in normal and stress conditions and the degradation pathways 7 , 11 – 14 require additional studies, in which the suggested method could be useful.…”

Section: Discussionmentioning

confidence: 99%

“…However, in later works, autophagy was demonstrated not to have a substantial effect on skin pigmentation 9 , and melanosomes were shown to be non-degradative 10 . Other mechanisms like inherent asymmetric localization of melanosomes between dividing keratinocytes could be potentially involved in a complex inhomogeneous distribution of melanin in the epidermis 11 – 13 . Hence, precise assessment of melanin distribution in different epidermal layers is required to study fundamental processes and identify melanin-related abnormalities in norm and pathology.…”

Section: Introductionmentioning

confidence: 99%

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Melanin distribution from the dermal–epidermal junction to the stratum corneum: non-invasive in vivo assessment by fluorescence and Raman microspectroscopy

Yakimov

Shirshin

Schleusener

et al. 2020

Sci Rep

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the fate of melanin in the epidermis is of great interest due to its involvement in numerous physiological and pathological processes in the skin. Melanin localization can be assessed ex vivo and in vivo using its distinctive optical properties. Melanin exhibits a characteristic Raman spectrum band shape and discernible near-infrared excited (NIR) fluorescence. However, a detailed analysis of the capabilities of depth-resolved confocal Raman and fluorescence microspectroscopy in the evaluation of melanin distribution in the human skin is lacking. Here we demonstrate how the fraction of melanin at different depths in the human skin in vivo can be estimated from its Raman spectra (bands at 1,380 and 1,570 cm −1) using several procedures including a simple ratiometric approach, spectral decomposition and non-negative matrix factorization. The depth profiles of matrix factorization components specific to melanin, collagen and natural moisturizing factor provide information about their localization in the skin. The depth profile of the collagen-related matrix factorization component allows for precise determination of the dermal-epidermal junction, i.e. the epidermal thickness. Spectral features of fluorescence background originating from melanin were found to correlate with relative intensities of the melanin Raman bands. We also hypothesized that NIR fluorescence in the skin is not originated solely from melanin, and the possible impact of oxidized species should be taken into account. The ratio of melanin-related Raman bands at 1,380 and 1,570 cm −1 could be related to melanin molecular organization. the proposed combined analysis of the Raman scattering signal and NIR fluorescence could be a useful tool for rapid non-invasive in vivo diagnostics of melanin-related processes in the human skin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Melanin distribution from the dermal–epidermal junction to the stratum corneum: non-invasive in vivo assessment by fluorescence and Raman microspectroscopy

Yakimov

Shirshin

Schleusener

et al. 2020

Sci Rep

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“…It’s known that several signaling pathways can regulate MITF, such as the MAPKs (ERK, JNK, and p38) signaling pathway ( Kim et al., 2017 ; Xu et al., 2018 ); the canonical Wnt signaling pathway, and the cAMP/PKA/CREB signaling pathway ( Wang et al., 2017b ; Yun et al., 2018 ). Besides, neighboring keratinocytes and fibroblasts have great impacts ( Joly-Tonetti et al., 2018 ; Koike et al., 2018 ). It is partly due to the effects of endocrine and paracrine cytokines secreted by keratinocytes and fibroblasts, such as alpha-melanocyte-stimulating hormone (α-MSH), stem cell factor (SCF) and endothelin1 (ET1) ( Pei et al., 2018 ; Yuan and Jin, 2018 ).…”

Section: Regulation Of Melanogenesismentioning

confidence: 99%

Traditional Asian Herbs in Skin Whitening: The Current Development and Limitations

Zeng

Huang

et al. 2020

Front. Pharmacol.

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In Asia, the market for whitening cosmetics is expanding rapidly, more and more people prefer to use natural products. Driven by natural product demand and technical advances, herbal research is also developing fast. Lots of studies reported that Asian herbal reagents can reduce melanogenesis, these findings provide evidence for the whitening application of Asian herbs. However, the current development status and challenges of herbal research need attention too. By reviewing these studies, different problems in studying herbal formulas, extracts, and active ingredients were presented. One of the most influential troubles is that the components of herbs are too complex to obtain reliable results. Thus, an understanding of the overall quality of herbal research is necessary. Further, 90 most cited Asian herbal studies on whitening were collected, which were conducted between 2017 and 2020, then statistical analysis was carried out. This work provided a comprehensive understanding of Asian herbal research in skin whitening, including the overall status and quality, as well as the focuses and limitations of these studies. By proactively confronting and analyzing these issues, it is suggested that the focus of herbal medicine research needs to shift from quantity to quality, and the new stage of development should emphasize transformation from research findings to whitening products.

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“…However, evidence indicates that the bulk of melanin is inherited only by the non‐differentiating daughter cell post mitosis in progenitor keratinocytes via asymmetric organelle inheritance. Moreover, this preferred pattern of melanin distribution can switch to a symmetric or equal daughter cell inheritance mode under conditions of stress .…”

Section: Introductionmentioning

confidence: 99%

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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An explanation for the mysterious distribution of melanin in human skin: a rare example of asymmetric (melanin) organelle distribution during mitosis of basal layer progenitor keratinocytes

Cited by 25 publications

References 34 publications

Melanin distribution from the dermal–epidermal junction to the stratum corneum: non-invasive in vivo assessment by fluorescence and Raman microspectroscopy

Melanin distribution from the dermal–epidermal junction to the stratum corneum: non-invasive in vivo assessment by fluorescence and Raman microspectroscopy

Traditional Asian Herbs in Skin Whitening: The Current Development and Limitations

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

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