Human skin and hair color are visible traits that can vary dramatically within and across ethnic populations. The genetic makeup of these traits-including polymorphisms in the enzymes and signaling ...proteins involved in melanogenesis, and the vital role of ion transport mechanisms operating during the maturation and distribution of the melanosome-has provided new insights into the regulation of pigmentation. A large number of novel loci involved in the process have been recently discovered through four large-scale genome-wide association studies in Europeans, two large genetic studies of skin color in Africans, one study in Latin Americans, and functional testing in animal models. The responsible polymorphisms within these pigmentation genes appear at different population frequencies, can be used as ancestry-informative markers, and provide insight into the evolutionary selective forces that have acted to create this human diversity.
Skin color diversity is the most variable and noticeable phenotypic trait in humans resulting from constitutive pigmentation variability. This paper will review the characterization of skin ...pigmentation diversity with a focus on the most recent data on the genetic basis of skin pigmentation, and the various methodologies for skin color assessment. Then, melanocyte activity and amount, type and distribution of melanins, which are the main drivers for skin pigmentation, are described. Paracrine regulators of melanocyte microenvironment are also discussed. Skin response to sun exposure is also highly dependent on color diversity. Thus, sensitivity to solar wavelengths is examined in terms of acute effects such as sunburn/erythema or induced-pigmentation but also long-term consequences such as skin cancers, photoageing and pigmentary disorders. More pronounced sun-sensitivity in lighter or darker skin types depending on the detrimental effects and involved wavelengths is reviewed.
As a main part of pigmentation disorders, skin depigmentation diseases such as vitiligo and achromic naevus are very common and get more attention now. The pathogenesis of depigmentation includes ...melanocyte dysfunction and loss, which are possibly caused by heredity, autoimmunity and oxidative stress. Among them, oxidative stress plays a key role; however, few clinical treatments can deal with oxidative stress. As reported, Cistanche deserticola polysaccharide (CDP) is an effective antioxidant; based on that, we evaluated its role in melanocyte and further revealed the mechanisms. In this study, we found that CDP could promote melanogenesis in human epidermal melanocytes (HEMs) and mouse melanoma B16F10 cells, it also induced pigmentation in zebrafish. Furthermore, CDP could activate mitogen‐activated protein kinase (MAPK) signal pathway, then up‐regulated the expression of microphthalmia‐associated transcription factor (MITF) and downstream genes TYR, TRP1, TRP2 and RAB27A. Otherwise, we found that CDP could attenuate H2O2‐induced cytotoxicity and apoptosis in melanocytes. Further evidence revealed that CDP could enhance NRF2/HO‐1 antioxidant pathway and scavenge intracellular ROS. In summary, CDP can promote melanogenesis and prevent melanocytes from oxidative stress injury, suggesting that CDP helps maintain the normal status of melanocytes. Thus, CDP may be a novel drug for the treatment of depigmentation diseases.
Cistanche deserticola polysaccharide (CDP) promotes melanogenesis in human epidermal melanocytes via activating mitogen‐activated protein kinase (MAPK) signal pathway, then up‐regulates the expression of MITF, TYR, TRP1, TRP2, and RAB27A. Otherwise, CDP can attenuate H2O2‐induced oxidative stress in melanocytes via enhancing NRF2/HO‐1 antioxidant pathway and scavenge intracellular ROS.
•Cutaneous pigmentation is regulated by a complex dermal-epidermal network.•Fibroblasts interact with melanocytes via the synthesis of biochemical factors.•Fibroblasts-derived factors bind to ...melanocyte receptors and modulate intracellular melanogenic pathways.•The importance of fibroblasts-derived factors is demonstrated by skin pigmentary changes.
Dermal fibroblasts are traditionally recognized as synthesizing, remodeling and depositing collagen and extracellular matrix, the structural framework for tissues, helping to bring thickness and firmness to the skin. However, the role of fibroblasts on skin pigmentation arouses concern recently. More is known about the interactions between epidermal melanocytes and keratinocytes.
This review highlights the importance of fibroblast-derived melanogenic paracrine mediators in the regulation of melanocyte activities. Fibroblasts act on melanocytes directly and indirectly through neighboring cells by secreting a large number of cytokines (SCF), proteins (DKK1, sFRP, Sema7a, CCN, FAP-α) and growth factors (KGF, HGF, bFGF, NT-3, NRG-1, TGF-β) which bind to receptors and modulate intracellular signaling cascades (MAPK/ERK, cAMP/PKA, Wnt/β-catenin, PI3K/Akt) related to melanocyte functions. These factors influence the growth, the pigmentation of melanocytes via the expression of melanin-producing enzymes and melanosome transfer, as well as their dendricity, mobility and adhesive properties. Thus, fibroblasts are implicated in both skin physiological and pathological pigmentation. In order to investigate their contribution, various in vitro models have been developed, based on cellular senescence. UV exposure, a major factor implicated in pigmentary disorders, may affect the secretory crosstalk between dermal and epithelial cells.
Therefore, identification of the interactions between fibroblasts and melanocytes could provide novel insights not only for the development of melanogenic agents in the clinical and cosmetic fields, but also for a better understanding of the melanocyte biology and melanogenesis regulation.
Canine coat pigmentation genetics: a review Brancalion, L.; Haase, B.; Wade, C. M.
Animal genetics,
February 2022, 2022-Feb, 2022-02-00, 20220201, Letnik:
53, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary
Our understanding of canine coat colour genetics and the associated health implications is developing rapidly. To date, there are 15 genes with known roles in canine coat colour phenotypes. ...Many coat phenotypes result from complex and/or epistatic genetic interactions among variants within and between loci, some of which remain unidentified. Some genes involved in canine pigmentation have been linked to aural, visual and neurological impairments. Consequently, coat pigmentation in the domestic dog retains considerable ethical and economic interest. In this paper we discuss coat colour phenotypes in the domestic dog, the genes and variants responsible for these phenotypes and any proven coat colour‐associated health effects.
The primary biological role of human skin pigmentation is as a mediator of penetration of ultraviolet radiation (UVR) into the deep layers of skin and the cutaneous circulation. Since the origin of ...Homo sapiens, dark, protective constitutive pigmentation and strong tanning abilities have been favored under conditions of high UVR and represent the baseline condition for modern humans. The evolution of partly depigmented skin and variable tanning abilities has occurred multiple times in prehistory, as populations have dispersed into environments with lower and more seasonal UVR regimes, with unique complements of genes and cultural practices. The evolution of extremes of dark pigmentation and depigmentation has been rare and occurred only under conditions of extremely high or low environmental UVR, promoted by positive selection on variant pigmentation genes followed by limited gene flow. Over time, the evolution of human skin pigmentation has been influenced by the nature and course of human dispersals and modifications of cultural practices, which have modified the nature and actions of skin pigmentation genes. Throughout most of prehistory and history, the evolution of human skin pigmentation has been a contingent and non‐deterministic process.
Skin pigmentation is a classic example of a polygenic trait that has experienced directional selection in humans. Genome-wide association studies have identified well over a hundred ...pigmentation-associated loci, and genomic scans in present-day and ancient populations have identified selective sweeps for a small number of light pigmentation-associated alleles in Europeans. It is unclear whether selection has operated on all of the genetic variation associated with skin pigmentation as opposed to just a small number of large-effect variants. Here, we address this question using ancient DNA from 1,158 individuals from West Eurasia covering a period of 40,000 y combined with genome-wide association summary statistics from the UK Biobank. We find a robust signal of directional selection in ancient West Eurasians on 170 skin pigmentation-associated variants ascertained in the UK Biobank. However, we also show that this signal is driven by a limited number of large-effect variants. Consistent with this observation, we find that a polygenic selection test in present-day populations fails to detect selection with the full set of variants. Our data allow us to disentangle the effects of admixture and selection. Most notably, a large-effect variant at
was introduced to Western Europe by migrations of Neolithic farming populations but continued to be under selection post-admixture. This study shows that the response to selection for light skin pigmentation in West Eurasia was driven by a relatively small proportion of the variants that are associated with present-day phenotypic variation.
Ultraviolet (UV)‐induced pigmentation is very common in clinical practice, but the current treatments are rarely effective, accompanied by some side effects. Ganoderma lucidum polysaccharide (GLP) is ...a natural antioxidant with no toxic side effects, which can antagonize UVB‐induced fibroblast photo aging. The study aims to explore the role of GLP in inhibiting UVB‐induced melanogenesis and its possible mechanism. The expression of melanogenesis genes such as microphthalmia‐associated transcription factor (MITF), tyrosine (TYR), tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2), ras‐related protein Rab‐27A (Rab27A), and Myosin shows an upward trend after exposure of B16F10 and PIG1 cells to UVB irradiation, but GLP can downregulate the expression of genes related to UVB‐induced melanogenesis. GLP can inhibit UVB‐activated protein kinase A (PKA) and mitogen‐activated protein kinase (MAPK) signaling pathways. Besides, GLP protects mitochondria from UVB damage and inhibits reactive oxygen species (ROS) production. Also, UVB‐induced cyclic adenosine monophosphate (cAMP) can be inhibited. It has been found in the experiments of UVB‐induced skin pigmentation in zebrafish that GLP is capable of inhibiting UVB‐induced skin pigmentation. Meanwhile, it can greatly relieve erythema reaction in guinea pig skin caused by high‐dosage UVB irradiation. In conclusion, this study shows that GLP can inhibit UVB‐induced melanogenesis by antagonizing cAMP/PKA and ROS/MAPK signaling pathways and is a potential natural safe whitening sunscreen additive.
This study is the first to explore the role of Ganoderma lucidum polysaccharide (GLP) in inhibiting Ultraviolet B (UVB)‐induced melanogenesis and its possible mechanism. we found that GLP could inhibit UVB‐induced melanogenesis by antagonizing cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and reactive oxygen species/mitogen‐activated protein kinase (ROS/MAPK) signaling pathways and is a potential natural safe whitening sunscreen additive
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