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Cleveland Clinic Journal of Medicine Jun 2022
Topics: Carney Complex; Humans; Myxoma; Skin Neoplasms; Skin Pigmentation
PubMed: 35649565
DOI: 10.3949/ccjm.89a.21069 -
The Journal of Investigative... Aug 2009Dickkopf 1 (DKK1), an inhibitor of Wnt signaling, not only functions as a head inducer during development, but also regulates joint remodeling and bone formation, which... (Review)
Review
Dickkopf 1 (DKK1), an inhibitor of Wnt signaling, not only functions as a head inducer during development, but also regulates joint remodeling and bone formation, which suggests roles for DKK1 in the pathogenesis of rheumatoid arthritis and multiple myeloma. We recently demonstrated that levels of DKK1 in palmoplantar dermal fibroblasts are physiologically higher than those observed in non-palmoplantar dermal fibroblasts. Thus, the DKK1-rich mesenchyme in palmoplantar dermis affects the overlying epithelium and induces a palmoplantar phenotype in the epidermis. More specifically, DKK1 suppresses melanocyte function and growth through the regulation of microphthalmia-associated transcription factor (MITF) and beta-catenin. Furthermore, DKK1 induces the expression of keratin 9 and alpha-Kelch-like ECT2-interacting protein (alphaKLEIP) but downregulates the expression of beta-catenin, glycogen synthase kinase 3beta, protein kinase C, and proteinase-activated receptor-2 (PAR-2) in keratinocytes. Treatment of reconstructed skin with DKK1 reproduces the hypopigmentation and thickening of skin through Wnt/beta-catenin signaling. These studies elucidate why human palmoplantar skin is thicker and paler than non-palmoplantar skin through the secretion of DKK1 by fibroblasts that affect the overlying epidermis. Thus, DKK1 may be useful for reducing skin pigmentation and for thickening photo-aged skin and palmoplantar wounds caused by diabetes mellitus and rheumatic skin diseases.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 73-75; doi:10.1038/jidsymp.2009.4.
Topics: Fibroblasts; Foot; Hand; Humans; Intercellular Signaling Peptides and Proteins; Keratinocytes; Melanocytes; Models, Biological; Signal Transduction; Skin; Skin Physiological Phenomena; Skin Pigmentation
PubMed: 19675559
DOI: 10.1038/jidsymp.2009.4 -
Indian Journal of Dermatology,... 2013Vitiligo is a common pigmentary disorder caused by the destruction of functional melanocytes. Vitamin D is an essential hormone synthesized in the skin and is... (Review)
Review
Vitiligo is a common pigmentary disorder caused by the destruction of functional melanocytes. Vitamin D is an essential hormone synthesized in the skin and is responsible for skin pigmentation. Low levels of vitamin D have been observed in vitiligo patients and in patients with other autoimmune diseases. Therefore, the relationship between vitamin D and vitiligo needs to be investigated more thoroughly. We reviewed the literature to date regarding the role of vitamin D in skin pigmentation. Our review revealed that vitamin D deficiency has been identified in many conditions, including premature and dysmature birth, pigmented skin, obesity, advanced age, and malabsorption. Vitamin D increases melanogenesis and the tyrosinase content of cultured human melanocytes by its antiapoptotic effect. However, a few growth-inhibitory effects on melanocytes were also reported. Vitamin D regulates calcium and bone metabolism, controls cell proliferation and differentiation, and exerts immunoregulatory activities. Vitamin D exerts its effect via a nuclear hormone receptor for vitamin D. The topical application of vitamin D increased the number of L-3,4-dihydroxyphenylalanine-positive melanocytes. The topical application of vitamin D yields significant results when used in combination with phototherapy and ultraviolet exposure to treat vitiligo in humans. Vitamin D decreases the expression of various cytokines that cause vitiligo. In conclusion, application of vitamin D might help in preventing destruction of melanocytes thus causing vitiligo and other autoimmune disorders. The association between low vitamin D levels and the occurrence of vitiligo and other forms of autoimmunity is to be further evaluated.
Topics: Animals; Humans; Melanocytes; Skin Pigmentation; Vitamin D; Vitamin D Deficiency; Vitiligo
PubMed: 24177606
DOI: 10.4103/0378-6323.120720 -
Hereditas 2018Skin color is a well-recognized adaptive trait and has been studied extensively in humans. Understanding the genetic basis of adaptation of skin color in various... (Review)
Review
BACKGROUND
Skin color is a well-recognized adaptive trait and has been studied extensively in humans. Understanding the genetic basis of adaptation of skin color in various populations has many implications in human evolution and medicine.
DISCUSSION
Impressive progress has been made recently to identify genes associated with skin color variation in a wide range of geographical and temporal populations. In this review, we discuss what is currently known about the genetics of skin color variation. We enumerated several cases of skin color adaptation in global modern humans and archaic hominins, and illustrated why, when, and how skin color adaptation occurred in different populations. Finally, we provided a summary of the candidate loci associated with pigmentation, which could be a valuable reference for further evolutionary and medical studies.
CONCLUSION
Previous studies generally indicated a complex genetic mechanism underlying the skin color variation, expanding our understanding of the role of population demographic history and natural selection in shaping genetic and phenotypic diversity in humans. Future work is needed to dissect the genetic architecture of skin color adaptation in numerous ethnic minority groups around the world, which remains relatively obscure compared with that of major continental groups, and to unravel the exact genetic basis of skin color adaptation.
Topics: Adaptation, Biological; Animals; Biological Evolution; Genetics, Population; Hominidae; Humans; Skin Pigmentation
PubMed: 28701907
DOI: 10.1186/s41065-017-0036-2 -
Proceedings of the National Academy of... Jan 2021Skin pigmentation is a classic example of a polygenic trait that has experienced directional selection in humans. Genome-wide association studies have identified well...
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.
Topics: Alleles; Asia; Asian People; Biological Evolution; DNA, Ancient; Databases, Genetic; Europe; Gene Frequency; Genome-Wide Association Study; Genotype; Haplotypes; Humans; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Selection, Genetic; Skin Pigmentation; White People
PubMed: 33443182
DOI: 10.1073/pnas.2009227118 -
BMC Genomics Dec 2022Aquatic animals show diverse body coloration, and the formation of animal body colour is a complicated process. Increasing evidence has shown that microRNAs (miRNAs)...
BACKGROUND
Aquatic animals show diverse body coloration, and the formation of animal body colour is a complicated process. Increasing evidence has shown that microRNAs (miRNAs) play important regulatory roles in many life processes. The role of miRNAs in pigmentation has been investigated in some species. However, the regulatory patterns of miRNAs in reptile pigmentation remain to be elucidated. In this study, we performed an integrated analysis of miRNA and mRNA expression profiles to explore corresponding regulatory patterns in embryonic body colour formation in the soft-shelled turtle Pelodiscus sinensis.
RESULTS
We identified 8 866 novel genes and 9 061 mature miRNAs in the skin of Chinese soft-shelled turtles in three embryonic stages (initial period: IP, middle period: MP, final period: FP). A total of 16 563 target genes of the miRNAs were identified. Furthermore, we identified 2 867, 1 840 and 4 290 different expression genes (DEGs) and 227, 158 and 678 different expression miRNAs (DEMs) in IP vs. MP, MP vs. FP, and IP vs. FP, respectively. Among which 72 genes and 25 miRNAs may be related to turtle pigmentation in embryonic development. Further analysis of the novel miRNA families revealed that some novel miRNAs related to pigmentation belong to the miR-7386, miR-138, miR-19 and miR-129 families. Novel_miR_2622 and novel_miR_2173 belong to the miR-19 family and target Kit and Gpnmb, respectively. The quantification of novel_miR_2622 and Kit revealed negative regulation, indicating that novel_miR_2622 may participate in embryonic pigmentation in P. sinensis by negatively regulating the expression of Kit.
CONCLUSIONS
miRNA act as master regulators of biological processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs and their target genes in Chinese soft-shelled turtle might be useful for investigating the molecular processes involved in pigmentation. All the results of this study may aid in the improvement of P. sinensis breeding traits for aquaculture.
Topics: Animals; Transcriptome; Turtles; MicroRNAs; Skin Pigmentation; Embryonic Development; China
PubMed: 36471254
DOI: 10.1186/s12864-022-09029-y -
International Journal of Environmental... Feb 2020Ultraviolet radiation (UVR) is a ubiquitous exposure which may contribute to decreased folate levels. Skin pigmentation mediates the biological effect of UVR exposure,...
Ultraviolet radiation (UVR) is a ubiquitous exposure which may contribute to decreased folate levels. Skin pigmentation mediates the biological effect of UVR exposure, but its relationship to folate levels is unexamined. Interactions may exist between UVR and pigmentation genes in determining folate status, which may, in turn, impact homocysteine levels, a potential risk factor for multiple chronic diseases. Therefore, independent and interactive influences of environmental UVR and genetic variants related to skin pigmentation (MC1R-rs1805007, IRF4-rs12203592 and HERC2-rs12913832) on folate (red blood cell (RBC) and serum) and homocysteine levels were examined in an elderly Australian cohort (n = 599). Genotypes were assessed by RT/RFLP-PCR, and UVR exposures were assessed as the accumulated erythemal dose rate accumulated over 4 months (4M-EDR). Multivariate analysis found significant negative associations between 4M-EDR and RBC folate (p < 0.001, β = -0.19), serum folate (p = 0.045, β = -0.08) and homocysteine levels (p < 0.001, β = -0.28). Significant associations between -rs1805007 and serum folate levels ( = 0.020), and -rs12203592 and homocysteine levels ( = 0.026) occurred but did not remain significant following corrections with confounders. No interactions between 4M-EDR and pigmentation variants in predicting folate/homocysteine levels were found. UVR levels and skin pigmentation-related variants are potential determinants of folate and homocysteine status, although, associations are mixed and complex, with further studies warranted.
Topics: Aged; Australia; Female; Folic Acid; Genotype; Homocysteine; Humans; Male; Skin; Skin Pigmentation; Ultraviolet Rays
PubMed: 32121219
DOI: 10.3390/ijerph17051545 -
BioMed Research International 2020This study reports the use of real-time PCR to identify the SNP rs1545397 in the intron region on the OCA2 gene from ancient and degraded DNA isolated from ancient human...
BACKGROUND
This study reports the use of real-time PCR to identify the SNP rs1545397 in the intron region on the OCA2 gene from ancient and degraded DNA isolated from ancient human bones from Mongolia, Korea, and Uzbekistan. This SNP is a marker for skin pigmentation. LightCycler-based probes (HybProbes) were designed. A LightCycler (version 2.0) system was used for the real-time PCR.
RESULTS
The results of the real-time PCRs of three different genotypes of SNP rs1545397 were compared with those of the direct sequencing. Melting curve analysis was used for genotype determination. Three genotypes were distinguished: the homozygous T (T/T) SNP type formed a distinct melting peak at 53.3 ± 0.14°C, the homozygous A (A/A) SNP type formed a distinct melting peak at 57.8 ± 0.12°C, and the heterozygous A/T SNP type formed two distinct melting peaks at 53.3 ± 0.17°C and 57.8 ± 0.15°C. Mongolian aDNA samples tested in this study carried all three types of the SNP (A/T, A/A, and T/T) with no distinctly predominant type observed. In contrast, Korean aDNA samples carried the Asian genotype (T/T), while the Uzbekistan aDNA samples carried the European genotype (A/A) more often than the Asian genotype (T/T).
CONCLUSIONS
Human Mongolian aDNA samples had A/T, A/A, and T/T SNP rs1545397 with no distinct predominant genotype. When combined with the archeological and aDNA studies of other coupling morphologies with aDNA, our results infer that Mongolia's prehistoric population had considerable heterogeneity of skin color and morphological traits and that in the Neolithic period, a Eurasian or mixed population inhabited the western part of Mongolia.
Topics: Asian People; DNA, Ancient; Genotype; Humans; Mongolia; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Republic of Korea; Skin Pigmentation; Uzbekistan
PubMed: 33083459
DOI: 10.1155/2020/2585324 -
American Journal of Clinical Dermatology Nov 2018The solar radiation range has harmful and beneficial effects. Sunscreens, which selectively block specific spectral regions, may potentially interfere with skin... (Review)
Review
The solar radiation range has harmful and beneficial effects. Sunscreens, which selectively block specific spectral regions, may potentially interfere with skin homeostasis. For instance, the ultraviolet (UV) B waveband produces erythema and DNA damage; simultaneously, it induces pre-vitamin D synthesis. UVA1 and visible light can both induce pigmentation in skin phototypes IV-VI, and act in synergy to induce erythema and persistent pigment darkening. In contrast, UVA may contribute to blood pressure control and cardioprotection by inducing release of nitric oxide from intracutaneous photolabile nitric oxide derivatives. Finally, infrared A radiation alters the collagen equilibrium of the dermal extracellular matrix but is involved in the regulation of body temperature and in nitric oxide release, with a potential beneficial impact on blood pressure regulation. Ideally, photoprotection should thus be performed with a neutral density filter, mitigating all radiation ranges homogeneously, to maintain solar spectrum homeostasis. Natural compounds such as mycosporine-like amino acids are promising natural UV radiation-filtering compounds for an improved homeostasis with our environment. Lastly, we should not forget individual characteristics and behavior, as homeostasis differs according to individual phototypes and skin exposure behaviors.
Topics: Administration, Cutaneous; Biological Variation, Population; Homeostasis; Humans; Skin; Skin Pigmentation; Sunlight; Sunscreening Agents; Ultraviolet Rays; Vitamin D
PubMed: 30374900
DOI: 10.1007/s40257-018-0369-2 -
JCI Insight Oct 2020Mottled skin pigmentation and solar lentigines from chronic photodamage with aging involve complex interactions between keratinocytes and melanocytes. However, the...
Mottled skin pigmentation and solar lentigines from chronic photodamage with aging involve complex interactions between keratinocytes and melanocytes. However, the precise signaling mechanisms that could serve as therapeutic targets are unclear. Herein, we report that expression of nuclear factor erythroid 2-related factor 2 (NRF2), which regulates reduction-oxidation reactions, is altered in solar lentigines and photodamaged skin. Moreover, mottled skin pigmentation in humans could be treated with topical application of the NRF2 inducer sulforaphane (SF). Similarly, UV light-induced pigmentation of WT mouse ear skin could be treated or prevented with SF treatment. Conversely, SF treatment was unable to reduce UV-induced ear skin pigmentation in mice deficient in NRF2 or in mice with keratinocyte-specific conditional deletion of IL-6Rα. Taken together, NRF2 and IL-6Rα signaling are involved in the pathogenesis of UV-induced skin pigmentation, and specific enhancement of NRF2 signaling could represent a potential therapeutic target.
Topics: Animals; Humans; Isothiocyanates; Keratinocytes; Melanocytes; Mice; NF-E2-Related Factor 2; Oxidation-Reduction; Receptors, Interleukin-6; Signal Transduction; Skin Aging; Skin Pigmentation; Sulfoxides; Ultraviolet Rays
PubMed: 33001866
DOI: 10.1172/jci.insight.139342