Vitamin D keratinocytes

BACKGROUND: Dysregulation of skin metabolism is associated with a plethora of diseases such as psoriasis and dermatitis. Until now, reconstructed human skin (RhS) models lack the metabolic potential of native human skin, thereby limiting their relevance to study human healthy and diseased skin. We aimed to determine whether incorporation of an adipocyte-containing hypodermis into RhS improves its metabolic potential and to identify major metabolic pathways up-regulated in adipose-RhS...

Methicillin-resistant biofilm-forming Staphylococcus spp. are found in about 25% of the overall cases of chronic wounds, which can undergo malignant degeneration and be associated with skin cancer. Although antimicrobial agents are clinically used to counteract pathogens and promote wound healing, they are increasingly ineffective against multi-drug resistant bacteria. Moreover, they can induce dysbiosis, which favors opportunistic pathogen infections and alters immune responses. Consequently, research on pathogen containment strategies is crucial...

BACKGROUND: Increasing evidence points at an important physiological role of the timekeeping system, known as the circadian clock (CC), regulating not only our sleep-awake rhythm but additionally many other cellular processes in peripheral tissues. It was shown in various cell types that environmental stressors, including ultraviolet B radiation (UV-B), modulate the expression of genes that regulate the CC (CCGs) and that these CCGs modulate susceptibility for UV-B-induced cellular damage...

Human skin is the natural source, place of metabolism, and target for vitamin D3 . The classical active form of vitamin D3 , 1,25(OH)2 D3 , expresses pluripotent properties and is intensively studied in cancer prevention and therapy. To define the specific role of vitamin D3 receptor (VDR) and its co-receptor retinoid X receptor alpha (RXRA) in genomic regulation, VDR or RXRA genes were silenced in the squamous cell carcinoma cell line A431 and treated with 1,25(OH)2 D3 at long incubation time points 24 h/72 h...

Vitamin D (VD) exerts a wide variety of biological functions including calcemic activity. VD nutritional status is closely associated with the onset and development of chronic diseases. To develop a VD analog with the desired VD activity but without calcemic activity, we screened synthetic VDR antagonists. We identified 1α,25-dihydroxyvitamin D3-26-23-lactams (DLAM)-2a-d (DLAM-2s) as nuclear vitamin D receptor (VDR) ligands in a competitive VDR binding assay for 1α,25(OH)2 vitamin D3 (1α,25(OH)2D3), and DLAM-2s showed an antagonistic effect on 1α,25(OH)2 D3-induced cell differentiation in HL60 cells...

Deregulation of mitochondria activity is one of the hallmarks of cancerogenesis and an important target for cancer therapy. Therefore, we compared the impact of an active form of vitamin D3 (1,25(OH)2 D3 ) on mitochondrial morphology and bioenergetics in human squamous cell carcinoma (A431) and immortalized HaCaT keratinocytes. It was shown that mitochondria of cancerous A431 cells differ from that observed in HaCaT keratinocytes in terms of network, morphology, bioenergetics, glycolysis, and mitochondrial DNA copy number, while treatment of A431 with 1,25(OH)2 D3 partially eliminates these differences...

With its unique anatomical location facing both the external and internal environment, the skin has crucial functions, including shielding the body from damage caused by ultraviolet radiation and chemicals, preventing water loss, acting as a primary barrier against pathogens, participating in metabolic processes like vitamin D production and temperature control and relaying information to the body through sensory and proprioceptor nerves. Like all organ systems, skin is known to undergo multiple changes with aging...

Topical medications represent the most commonly used drugs in the treatment of psoriasis. However, topical steroids are mainly limited to short-term or intermittent use, and traditional non-steroidal topicals such as vitamin D analogues, topical calcineurin inhibitors, and topical retinoids are limited by low efficacy and poor local skin tolerability. Tapinarof (GSK2894512, DMVT-505) is a novel, topical aryl hydrocarbon receptor (AHR) agonist, which was recently approved by the FDA for the treatment of plaque psoriasis in adults...

The adverse effects of solar ultraviolet radiation (UVR) on normal skin are well established, especially in those with poorly melanized skin. Clinically, these effects may be classified as acute, such as erythema or chronic such as keratinocyte and melanocyte skin cancers. Apart from skin type genetics, clinical responses to solar UVR are dependent on geophysical (e.g., solar intensity) and behavioural factors. The latter are especially important because they may result in 'solar overload' with unwanted clinical consequences and ever greater burdens to healthcare systems...

It is well known that vitamin D is engaged in calcium and phosphorus metabolism. However, vitamin D also plays an important role in other aspects over the past decades, such as immune response. Vitamin D has thus aroused the interest of the scientific community, especially the field of dermatology. The major source of vitamin D comes from the exposure of the skin to ultraviolet B. In turn, vitamin D regulates the proliferation and differentiation of keratinocytes, prevents opportunistic infection, and regulates the inflammatory response and immune response of the skin...

Calcipotriol (calcipotriene) is a synthetic vitamin D3 derivative that is a standard treatment option for psoriasis. It is generally well tolerated with minimal side effects. Due to its ability to reduce keratinocyte proliferation and induce keratinocyte differentiation as well as its immunomodulatory effects, calcipotriol has been used to treat a variety of skin disorders such as atopic dermatitis, actinic keratoses, lichen planus, seborrheic keratoses, and vitiligo [1]. We surveyed the literature examining the use of calcipotriol for non-psoriatic dermatologic disease...

BACKGROUND/PURPOSE: Psoriasis is a multifactorial disease. It is a combination of genetic, immunological, and environmental factors. Vitamin D receptor (VDR) is a nuclear receptor that regulates epidermal cell growth through the inhibition of proliferation and induction of keratinocytes terminal differentiation. Aim of the study was to investigate the effect of Narrow-band UVB (NB-UVB) therapy on VDR expression in the skin of psoriasis patients. MATERIALS AND METHODS: Forty patients with different severities of psoriasis were assessed using the psoriasis area and severity index (PASI) score...

BACKGROUND: The vitamin D receptor (VDR) has a low level of expression in the keratinocytes of patients with psoriasis and plays a role in the development of the disease. Furthermore, the crosstalk between macrophages and psoriatic keratinocytes-derived exosomes is critical for psoriasis progression. However, the effects of VDR-deficient keratinocytes-derived exosomes (Exos-shVDR) on macrophages and their underlying mechanisms remain largely unknown. METHODS: VDR-deficient keratinocytes were constructed by infecting HaCaT cells with a VDR-targeting lentivirus, mimicking the VDR-deficient state observed in psoriatic keratinocytes...

An active form of vitamin D3 (1,25-dihydroxyvitamin D3 ) acts through vitamin D receptor (VDR) initiating genomic response, but several studies described also non-genomic actions of 1,25-dihydroxyvitamin D3 , implying the role of PDIA3 in the process. PDIA3 is a membrane-associated disulfide isomerase involved in disulfide bond formation, protein folding, and remodeling. Here, we used a transcriptome-based approach to identify changes in expression profiles in PDIA3-deficient squamous cell carcinoma line A431 after 1,25-dihydroxyvitamin D3 treatment...

The hormonal form of vitamin D3 , 1,25(OH)2 D3 , reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D3 production in the skin, and continued UV exposure photoisomerizes pre-vitamin D3 to produce "over-irradiation products" such as lumisterol3 (L3 ). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L3 to produce three main derivatives: 24-hydroxy-L3 [24(OH)L3 ], 22-hydroxy-L3 [22(OH)L3 ], and 20,22-dihydroxy-L3 [20,22(OH)L3 ]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L3 , in human primary keratinocytes and human skin explants...

Vitamin D receptor (VDR) exerts its biological effects when it heterodimerizes to a nuclear receptor of the retinoid family called retinoid X receptor α (RXRα), stimulating or inhibiting DNA transcription. VDR stimulation by vitamin D analogs led to in vitro antiproliferative effects, and experimental RXRα knockout led to loss of proliferation control in melanoma cells. The aim of this study was to determine VDR and RXRα positivity in melanocytic lesions, compared with normal skin species...

Incidence rates of melanoma and keratinocyte skin cancers have been on the rise globally in recent decades. While there has been a select focus on personal sun protection awareness, to our knowledge, there is a paucity of legislation in place to help support citizens' efforts to protect themselves from the harmful effects of ultraviolet radiation (UVR). Given this, we conducted a comprehensive review of legislation and guidelines pertaining to a variety of sun protection-related topics in countries of the Group of Seven (G7), Australia and New Zealand...

Although the management options for psoriasis have progressed with the use of systemic agents, there are few efficacious nonsteroidal topical therapies for patients with limited or lower grade disease. The effects of allopurinol (Allo) and glutathione (GSH) were examined in two different in vitro models for psoriasis. In the first model, human immortalized keratinocytes (HaCaT) were treated with M5 cocktail (IL-17A, IL-22, oncostatin M, IL-1 α , and TNF- α ) in four interventional groups (control, Allo, oxypurinol (Oxy), and methotrexate (MTX))...

Keloids are disfiguring fibroproliferative lesions that can occur in susceptible individuals following any skin injury. They are extremely challenging to treat, with relatively low response rates to current therapies and high rates of recurrence after treatment. Although several distinct genetic loci have been associated with keloid formation in different populations, there has been no single causative gene yet identified and the molecular mechanisms guiding keloid development are incompletely understood. Further, although it is well known that keloids are more commonly observed in populations with dark skin pigmentation, the basis for increased keloid risk in skin of colour is not yet known...

The process of human embryonic mammary development gives rise to the structures in which mammary cells share a developmental lineage with skin epithelial cells such as keratinocytes. As some breast carcinomas have previously been shown to express high levels of involucrin, a marker of keratinocyte differentiation, we hypothesised that some breast tumours may de-differentiate to a keratinocyte-derived 'evolutionary history'. To confirm our hypothesis, we investigated the frequency of involucrin expression along with that of Brk, a tyrosine kinase expressed in up to 86% of breast carcinomas whose normal expression patterns are restricted to differentiating epithelial cells, most notably those in the skin (keratinocytes) and the gastrointestinal tract...