Extraciliary OFD1 Is Involved in Melanocyte Survival through Cell Adhesion to ECM via Paxillin.

Primary cilia play a significant role in influencing cell fate, including apoptosis in multiple cell types. In the lesional epidermis of vitiligo patients, a reduced number of ciliated cells was observed. Our study also revealed a downregulation of oral-facial digital syndrome type 1 (OFD1) in the affected skin of vitiligo patients.

Oxidative Stress Induces Skin Pigmentation in Melasma by Inhibiting Hedgehog Signaling.

There is growing evidence that oxidative stress plays a role in melasma and disrupts primary cilia formation. Additionally, primary cilia have been suggested to have an inhibitory role in melanogenesis. This study examined the potential link between oxidative stress, skin hyperpigmentation, and primary cilia.

Aquaporin-3 Downregulation in Vitiligo Keratinocytes Increases Oxidative Stress of Melanocytes.

Oxidative stress-induced melanocyte apoptosis is linked to the immune system and plays a critical role in the pathogenesis of vitiligo. Aquaporin-3 (AQP3), which is downregulated in vitiligo keratinocytes, regulates intracellular HO accumulation. However, the role of AQP3 in oxidative stress is uncertain in vitiligo.

Growth Factors Upregulated by Uric Acid Affect Guanine Deaminase-Induced Melanogenesis.

Uric acid produced by guanine deaminase (GDA) is involved in photoaging and hyperpigmentation. Reactive oxygen species (ROS) generated by uric acid plays a role in photoaging. However, the mechanism by which uric acid stimulates melanogenesis in GDA-overexpressing keratinocytes is unclear.

Anti-Tumor Effect of IDF-11774, an Inhibitor of Hypoxia-Inducible Factor-1, on Melanoma.

Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it.

Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2.

Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders.

IL-1 Receptor Antagonist Reduced Chemical-Induced Keratinocyte Apoptosis through Antagonism to IL-1α/IL-1β.

Extracellular interleukin 1 alpha (IL-1α) released from keratinocytes is one of the endpoints for assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-1α is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals.

An Acrodermatitis Enteropathica-Associated Zn Transporter, ZIP4, Regulates Human Epidermal Homeostasis.

Acrodermatitis enteropathica is an autosomal recessive disorder characterized by scaly eczematous dermatosis accompanied by alopecia and diarrhea. Various mutations in the SLC39A4 gene (ZIP4), which encodes a zinc transporter, are responsible for this disorder. However, the molecular mechanism underlying the involvement of ZIP4 in the pathogenesis of this condition has yet to be established.

Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity.

Skin melanocytes are activated by exposure to UV radiation to secrete melanin-containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known.

Cadherin 11 Involved in Basement Membrane Damage and Dermal Changes in Melasma.

Basement membrane (BM) disruption and dermal changes (elastosis, collagenolysis, vascular ectasia) have been reported in melasma. Although ultraviolet (UV) irradiation can induce these changes, UV is not always necessary for melasma development. Cadherin 11 (CDH11), which is upregulated in some melasma patients, has previously been shown to stimulate melanogenesis.

Cadherin 11, a miR-675 target, induces N-cadherin expression and epithelial-mesenchymal transition in melasma.

Cadherin 11 (CDH11) was identified as a target of miR-675 by using a luciferase reporter assay. CDH11 expression and miR-675 expression were inversely correlated. CDH11 expression was not detected in melanocytes, but CDH11 expression in fibroblasts and keratinocytes positively influenced melanogenesis via the canonical Wnt and AKT activation pathways in cocultured melanocytes.

Reduced MiR-675 in exosome in H19 RNA-related melanogenesis via MITF as a direct target.

H19 non-coding RNA downregulation stimulates melanogenesis in melasma patients. However, its mechanism is unclear. In this study, the potential role of a H19 microRNA, miR-675, in melanogenesis was examined.

Three new single nucleotide polymorphisms identified by a genome-wide association study in Korean patients with vitiligo.

Genetic susceptibility is involved in the pathogenesis of vitiligo. Association studies with a whole genome-based approach instead of a single or a few candidate genes may be useful for discovering new susceptible genes. Although the etiology of non-segmental and segmental types is different, the association between gene polymorphisms and vitiligo has been reported, without defining types or in non-segmental type.

Antiphotoaging effects of light-emitting diode irradiation on narrow-band ultraviolet B-exposed cultured human skin cells.

Background: Antiaging effects of light-emitting diodes (LEDs) have been clinically demonstrated using one or two wavelengths. The mechanism is unclear.

Objective: To examine direct and indirect photobiomodulation effects of LEDs on narrow-band ultraviolet B (NB-UVB)-induced photoaging using seven different wavelengths alone or in combination.

PDZK1 upregulation in estrogen-related hyperpigmentation in melasma.

The pathogenesis of melasma is unknown, although the potential role of estrogen has been considered. Microarray and real-time PCR analyses revealed that upregulation of PDZ domain protein kidney 1 (PDZK1) is clinically correlated with melasma. Although there has been no report that PDZK1 is involved in pigmentation and/or melanogenesis, PDZK1 expression can be induced by estrogen.

Light-emitting diodes at 830 and 850 nm inhibit melanin synthesis in vitro.

Treatment of hyperpigmentation remains a challenge. Because of the positive effects of low-energy Nd:YAG lasers on the treatment of melasma, it is suggested that laser-like light-emitting diodes (LEDs) can potentially ameliorate hyperpigmentation. We evaluated the effect of seven different LED wavelengths on melanogenesis.

Histamine effect on melanocyte proliferation and vitiliginous keratinocyte survival.

Repigmention of vitiligo requires melanocyte proliferation and migration. Keratinocytes have been shown to play a role in this process. Data from this laboratory showed that bee venom (BV) stimulated melanocyte proliferation and migration as well as melanogenesis.

Reduced aquaporin3 expression and survival of keratinocytes in the depigmented epidermis of vitiligo.

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway is critical for the survival of differentiating cells and depends on the E-cadherin-catenin complex. In an earlier study we showed impaired PI3K/AKT activation in vitiliginous keratinocytes (KCs). Recently, aquaporin3 (AQP3) has been reported to co-accumulate with E-cadherin in forming cell-to-cell contacts.

H19 RNA downregulation stimulated melanogenesis in melasma.

A variety of factors, including ultraviolet (UV) exposure, have been implicated in the pathogenesis of melasma. However, UV-induced hyperpigmentation usually recovers spontaneously, whereas melasma does not. Recently, we detected downregulation of the H19 gene on microarray analysis of hyperpigmented and normally pigmented skin from patients with melasma, and identified significant clinical correlations.

Lotus (Nelumbo nuficera) flower essential oil increased melanogenesis in normal human melanocytes.

In this study, the essential oil from lotus flower extract, including petals and stamens, was assessed with regard to its effects on melanogenesis in human melanocytes. The lotus flower essential oil was shown to stimulate melanin synthesis and tyrosinase activity in a dose-dependent manner. The lotus flower essential oil induced the expression of tyrosinase, microphthalmia-associated transcription factor M (MITF-M), and tyrosinase-related proten-2 (TRP-2) proteins, but not tyrosinase mRNA.

Stem cell factor induces ERM proteins phosphorylation through PI3K activation to mediate melanocyte proliferation and migration.

Stem cell factor (SCF) activates a variety of signals associated with stimulation of proliferation, differentiation, migration, and survival in melanocytes. However, the molecular mechanisms by which SCF and its receptor Kit activates these signaling pathways simultaneously and independently are still poorly defined. Here, we examined whether SCF induces ezrin/radixin/moesin (ERM) proteins phosphorylation as a downstream target of PI3K in melanocytes.

Bee venom stimulates human melanocyte proliferation, melanogenesis, dendricity and migration.

Pigmentation may result from melanocyte proliferation, melanogenesis, migration or increases in dendricity. Recently, it has been reported that secreted phospholipase A(2)(sPLA(2)) known as a component of bee venom (BV), stimulates melanocyte dendricity and pigmentation. BV has been used clinically to control rheumatoid arthritis and to ameliorate pain via its anti-inflammatory and antinociceptive properties.

Impaired PI3K/Akt activation-mediated NF-kappaB inactivation under elevated TNF-alpha is more vulnerable to apoptosis in vitiliginous keratinocytes.

Levels of the cytokines IL-6, IL-1alpha, and tumor necrosis factor-alpha (TNF-alpha) are significantly higher in lesional than in non-lesional skin of patients with vitiligo. However, how cytokines affect pigmentation is not fully understood. To examine the mechanism, Western blot analysis with TNF-alpha, Fas ligand (FasL), and downstream signaling molecules such as I-kappaB, NF-kappaB, TNF-R1-associated factor 2, Akt, and PTEN (phosphatase and tension homologue) were performed for the suction-blistered depigmented and normally pigmented epidermis from 10 patients.

Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo.

Stem cell factor (SCF) of keratinocyte origin regulates melanocyte growth and survival. Deprivation of survival factors causes the apoptosis of melanocytes. Vitiligo often develops following physical trauma, even if this is minor.