-
Current Molecular Medicine 2023Vitiligo is the utmost common depigmenting condition consequential from melanocyte loss from the basal layer of the epidermis. Vitiligo disease mostly affects...
Vitiligo is the utmost common depigmenting condition consequential from melanocyte loss from the basal layer of the epidermis. Vitiligo disease mostly affects dark-skinned races and makes them more sensitive to UV radiation. It is also linked with some autoimmune diseases and various psychosocial difficulties. Melanocyte loss leads to depigmentation in vitiligo, is a major concern over decades, and even affects an individual's day-to-day life severely. All the theories, including autoimmune, autocytotoxic, and neural, collectively decipher either prime impact on the melanogenesis inhibition or deficient adhesion inspired melanocytes disappearance. Previously it has been described that melanocyte loss in vitiligo patients is caused by defective adhesion. Melanocyte death by apoptosis mainly occurs due to melanocyte detachment or migration from the basal layer and further followed by transepidermal migration. Various cell surface molecules, i.e., cell adhesion molecules (CAMs) in affiliation with neighbouring cells and extracellular matrix (ECM), encompass a typical cell adhesion process. All these ECM molecules along with transcription factors, help in the survival and maintenance of pigmentary cells/melanocytes. Therefore, in this issue, we have tried to compile the literature available on melanocyte detachment/apoptosis in ECM due to the alteration in adhesion molecules and matrix metalloproteinases (MMPs) driven by known/unknown transcription factors.
Topics: Humans; Vitiligo; Cell Adhesion; Melanocytes; Apoptosis; Transcription Factors
PubMed: 35726816
DOI: 10.2174/1566524022666220621125552 -
Cells Sep 2022Autophagy is a vital process for cell survival and it preserves homeostasis by recycling or disassembling unnecessary or dysfunctional cellular constituents. Autophagy... (Review)
Review
Autophagy is a vital process for cell survival and it preserves homeostasis by recycling or disassembling unnecessary or dysfunctional cellular constituents. Autophagy ameliorates skin integrity, regulating epidermal differentiation and constitutive pigmentation. It induces melanogenesis and contributes to skin color through melanosome turnover. Autophagy activity is involved in skin phenotypic plasticity and cell function maintenance and, if altered, it concurs to the onset and/or progression of hypopigmentary and hyperpigmentary disorders. Overexpression of autophagy exerts a protective role against the intrinsic metabolic stress occurring in vitiligo skin, while its dysfunction has been linked to the tuberous sclerosis complex hypopigmentation. Again, autophagy impairment reduces melanosome degradation by concurring to pigment accumulation characterizing senile lentigo and melasma. Here we provide an updated review that describes recent findings on the crucial role of autophagy in skin pigmentation, thus revealing the complex interplay among melanocyte biology, skin environment and autophagy. Hence, targeting this process may also represent a promising strategy for treating pigmentary disorders.
Topics: Autophagy; Humans; Hypopigmentation; Melanocytes; Pigmentation Disorders; Skin Pigmentation
PubMed: 36230960
DOI: 10.3390/cells11192999 -
Journal of Cellular Physiology Sep 2023Ultraviolet (UV) radiation is the primary exogenous inducer of skin pigmentation, although the mechanism has not been fully elucidated. N6-methyladenosine (m A)...
Ultraviolet (UV) radiation is the primary exogenous inducer of skin pigmentation, although the mechanism has not been fully elucidated. N6-methyladenosine (m A) modification is one of the key epigenetic form of gene regulation that affects multiple biological processes. The aim of this study was to explore the role and underlying mechanisms of m A modification in UVB-induced melanogenesis. Low-dose UVB increased global m A modification in melanocytes (MCs) and MNT1 melanoma cell line. The GEPIA database predicted that methyltransferase METTL3 is positively correlated with the melanogenic transcription factor MITF in the sun-exposed skin tissues. After METTL3 respectively overexpressed and knocked down in the MNT1, the melanin content and melanogenesis-related genes were significantly upregulated after overexpression of METTL3, especially with UVB irradiation, and downregulated after METTL3 knockdown. METTL3 levels were also higher in melanocytic nevi with high melanin content. METTL3 overexpression and knockdown also altered the protein level of YAP1. SRAMP analysis predicted four high-potential m A modification sites on YAP1 mRNA, of which three were confirmed by methylated RNA immunoprecipitation. Inhibition of YAP1 expression can partially reverse melanogenesis induced by overexpression of METTL3. In conclusion, UVB irradiation promotes global m A modification in MCs and upregulates METTL3, which increases the expression level of YAP1 through m A modification, thereby activating the co-transcription factor TEAD1 and promoting melanogenesis.
Topics: Humans; Melanins; Melanocytes; Methyltransferases; Transcription Factors; Ultraviolet Rays; Cell Line, Tumor
PubMed: 37417881
DOI: 10.1002/jcp.31077 -
Stem Cells and Development Mar 2022Skin bears essential appendages and diverse cell types that function importantly in protection, thermoregulation, mechanosensation, piloerection, and social...
Skin bears essential appendages and diverse cell types that function importantly in protection, thermoregulation, mechanosensation, piloerection, and social communication. The hair follicle is a tiny skin appendage with intricate structure and has versatile functions in mammals. Hair follicles evolve stem cells that regenerate cyclically to produce hairs and to accommodate the rapidly changing environment. Sharing the same bulge niche with hair follicle stem cells (HFSCs), melanocyte stem cells (McSCs) undergo cyclic activation in synchrony with HFSCs, to pigment the hairs, which can protect the skin from ultraviolet radiation. Disorders of HFSCs or McSCs result in skin diseases such as hair loss, canities, vitiligo, and even melanoma, compromising senses of well-being and posing psychosocial distress to the affected individuals. The activation or quiescence of these stem cells is not only regulated by intrinsic factors within the follicle, but is also largely influenced by the extrinsic environmental factors, including the neighboring cells, systemic factors, and the external environment. Although great progress has been made to elucidate the intrinsic regulation of HFSCs or McSCs, understanding the environmental modulation of these stem cells can provide novel insight for the development of new therapeutic strategies for treating alopecia and skin pigmentation-related disorders.
Topics: Alopecia; Animals; Hair; Hair Follicle; Humans; Mammals; Melanocytes; Skin Pigmentation; Ultraviolet Rays
PubMed: 35285756
DOI: 10.1089/scd.2022.29011.wwu -
Journal of the European Academy of... Nov 2023Mitochondria has emerged as a potential modulator of melanocyte function other than just meeting its cellular ATP demands. Mitochondrial DNA defects are now an... (Review)
Review
Mitochondria has emerged as a potential modulator of melanocyte function other than just meeting its cellular ATP demands. Mitochondrial DNA defects are now an established cause of maternal inheritance diseases. Recent cellular studies have highlighted the mitochondrial interaction with other cellular organelles that lead to disease conditions such as in Duchenne muscular dystrophy, where defective mitochondria was found in melanocytes of these patients. Vitiligo, a depigmentory ailment of the skin, is another such disorder whose pathogenesis is now found to be associated with mitochondria. The complete absence of melanocytes at the lesioned site in vitiligo is a fact; however, the precise mechanism of this destruction is still undefined. In this review we have tried to discuss and link the emerging facts of mitochondrial function or its inter- and intra-organellar communications in vitiligo pathogenesis. Mitochondrial close association with melanosomes, molecular involvement in melanocyte-keratinocyte communication and melanocyte survival are new paradigm of melanogenesis that could ultimately account for vitiligo. This definitely adds the new dimensions to our understanding of vitiligo, its management and designing of future mitochondrial targeted therapy for vitiligo.
Topics: Humans; Vitiligo; Melanocytes; Hypopigmentation; Skin; Mitochondria
PubMed: 36897230
DOI: 10.1111/jdv.19019 -
European Journal of Dermatology : EJD Dec 2020Hyperpigmentation and hypopigmentation are two manifestations of skin pigmentation diseases. Recent studies have shown that autophagy is involved in the development of... (Review)
Review
Hyperpigmentation and hypopigmentation are two manifestations of skin pigmentation diseases. Recent studies have shown that autophagy is involved in the development of skin pigmentation diseases. The melanosome is a lysosome-related organelle characterized by the production of melanin. The autophagosome-lysosome degradation pathway exhibits a characteristic cell renewal function. The functions of melanosomes and autophagosomes intersect and the vesicle transport pathway mediates both autophagosome and melanosome formation, which may involve different regulatory protein complexes. Current studies have revealed that several autophagy-related regulators of autophagosome formation are involved in melanosome formation and maturation and also regulate melanogenesis, and that melanosomes can be degraded via autophagy in melanocytes. Autophagy is also involved in regulating the living environment of melanocytes. Understanding the effects of autophagy on pigmentation may support our understanding of pigmentation diseases. This article reviews the relationship between autophagy and pigmentation in melanocytes.
Topics: Autophagy; Humans; Melanocytes; Melanosomes; Pigmentation Disorders; Skin Pigmentation
PubMed: 33262098
DOI: 10.1684/ejd.2020.3930 -
Cells Jun 2022Pigmentation is an important process in skin physiology and skin diseases and presumably also plays a role in Parkinson's disease (PD). In PD, alpha-Synuclein (aSyn) has...
Pigmentation is an important process in skin physiology and skin diseases and presumably also plays a role in Parkinson's disease (PD). In PD, alpha-Synuclein (aSyn) has been shown to be involved in the pigmentation of neurons. The presynaptic protein is intensively investigated for its pathological role in PD, but its physiological function remains unknown. We hypothesized that aSyn is both involved in melanocytic differentiation and melanosome trafficking processes. We detected a strong expression of aSyn in human epidermal melanocytes (NHEMs) and observed its regulation in melanocytic differentiation via the microphthalmia-associated transcription factor (MITF), a central regulator of differentiation. Moreover, we investigated its role in pigmentation by performing siRNA experiments but found no effect on the total melanin content. We discovered a localization of aSyn to melanosomes, and further analysis of aSyn knockdown revealed an important role in melanocytic morphology and a reduction in melanosome release. Additionally, we found a reduction of transferred melanosomes in co-culture experiments of melanocytes and keratinocytes but no complete inhibition of melanosome transmission. In summary, this study highlights a novel physiological role of aSyn in melanocytic morphology and its so far unknown function in the pigment secretion in melanocytes.
Topics: Humans; Keratinocytes; Melanins; Melanocytes; Melanosomes; alpha-Synuclein
PubMed: 35805172
DOI: 10.3390/cells11132087 -
Polski Merkuriusz Lekarski : Organ... Feb 2022Melanogenesis disorder is called dyschromia, is involved in various conditions including vitiligo, solar lentigo, and melanoma, the last of which is the most malignant...
UNLABELLED
Melanogenesis disorder is called dyschromia, is involved in various conditions including vitiligo, solar lentigo, and melanoma, the last of which is the most malignant type of skin cancer.
AIM
The aim of study was focused on histological visualization of melanogenic system.
MATERIALS AND METHODS
To investigate the roles of melanocytes and melanin, we used a rat skin as an experimental animal. Samples were stained using hematoxylin-eosin, the Schmorl's technique, the Fontana-Masson technique, the Warthin-Starry technique, and the S100 immunohistochemistry marker technique. Microscopy images were analyzed using the ImageJ free software protocol.
RESULTS
We found Fontana-Masson staining to be the most suitable for obtaining reliable results compared with the other methods, which had more disadvantages. We also found the S100 marker staining to be an effective tool for measuring the melanocyte count.
CONCLUSIONS
We consider the ImageJ processing protocol and staining procedures to be useful tools to estimate melanin and melanocyte pathology.
Topics: Animals; Melanins; Melanocytes; Melanoma; Rats; Skin Neoplasms; Vitiligo
PubMed: 35278293
DOI: No ID Found -
Journal of the European Academy of... Nov 2023Vitiligo is a common chronic skin disease which has an adverse impact on patients' life. Its pathogenesis is complex, involving autoimmunity and oxidative stress (OS).... (Review)
Review
Vitiligo is a common chronic skin disease which has an adverse impact on patients' life. Its pathogenesis is complex, involving autoimmunity and oxidative stress (OS). Autoimmunity leads to the loss of epidermal melanocytes and the formation of the depigmented patches of the disease. Treatment of vitiligo should control the exaggerated immune response to arrest the progress of active disease, and then promote melanocytes to repigmentation. Wnt/β-catenin signalling pathway has been of recent interest in vitiligo. Wnt/β-catenin signalling pathway is downregulated in vitiligo. Upregulation of Wnt/β-catenin signalling possibly control vitiligo autoimmune response by protecting melanocyte from OS damage, inhibiting CD8 T cell effector cell differentiation and enhancing Treg. Wnt/β-catenin signalling plays a critical role in the melanocyte regeneration by driving the differentiation of melanocyte stem cells (McSCs) into melanocytes. Promoting Wnt/β-catenin signalling can not only arrest the progress of active disease of vitiligo but also promote repigmentation. Some of the main effective therapies for vitiligo are likely to work by activating Wnt/β-catenin signalling. Agents that can enhance the effect of Wnt/β-catenin signalling may become potential candidates for the development of new drugs for vitiligo treatment.
Topics: Humans; Vitiligo; beta Catenin; Hypopigmentation; Melanocytes; Epidermis
PubMed: 36912722
DOI: 10.1111/jdv.19022 -
Pigment Cell & Melanoma Research Nov 2020Vitiligo is the most common acquired pigmentary disorder, which afflicts 0.5%-1% of the world population, and is characterized by depigmented skin patches resulting from... (Review)
Review
Vitiligo is the most common acquired pigmentary disorder, which afflicts 0.5%-1% of the world population, and is characterized by depigmented skin patches resulting from melanocyte loss. Vitiligo has a complex etiology and varies in its manifestations, progression, and response to treatment. It presents as an autoimmune disease, evidenced by circulating melanocyte-specific antibodies, and association with other autoimmune diseases. However, autoimmunity may be secondary to the high oxidative stress in vitiligo skin and to intrinsic defects in melanocytes and their microenvironment, which contribute to aberrant stress response, neo-antigenicity, and susceptibility of melanocytes to immune attack and apoptosis. There is also a genetic predisposition to vitiligo, which sensitizes melanocytes to environmental agents, such as phenolic compounds. Currently, there are different treatment modalities for re-pigmenting vitiligo skin. However, when repigmentation is achieved, the major challenge is maintaining the pigmentation, which is lost in 40% of cases. In this review, we present an overview of the clinical aspects of vitiligo, its pathophysiology, the intrinsic defects in melanocytes and their microenvironment, and treatment strategies. Based on lessons from the biology of human melanocytes, we present our perspective of how repigmentation of vitiligo skin can be achieved and sustained.
Topics: Autoimmunity; Cellular Microenvironment; Humans; Melanocytes; Oxidative Stress; Vitiligo
PubMed: 32198977
DOI: 10.1111/pcmr.12878