Topical Vitamin D Receptor Antagonist/Partial-Agonist Treatment Induces Epidermal Hyperproliferation via RARγ Signaling Pathways

Lucas, Renata; Mihály, Johanna; Gericke, Janine; Lera, Ángel R. de; Álvarez, Susana; Veleczki, Zsuzsanna; Törőcsik, Dániel; Rühl, Ralph

doi:10.1159/000508334

Cited by 3 publications

(3 citation statements)

References 47 publications

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“…Our results suggest that the increased levels of these bioactive derivatives and thereby further active VDR-RXR-mediated signalling may correlate well with clinical AD markers [54]. These data suggest that the negative correlation of 25(OH)D 3 plasma levels with clinical AD markers might just indicate reduced plasma levels of 25(OH)D 3 due to an increased metabolism towards 1,25(OH) 2 D 3 and further pro-allergic signalling [26-30]. In consequence, a supplementation with additional vitamin D might be likely detrimental as displayed in studies performing vitamin D supplementations to allergy and AD patients [16-18] and the consequence that an additional vitamin D supplementation might result in a simple maintenance or even an aggravation of the chronic AD status.…”

Section: Discussionmentioning

confidence: 99%

“…Controversies exist also when focusing on mice. Vitamin D receptor (VDR)-deficient mice obtain an increased transepidermal water-loss and barrier properties [25], while topical VDR-ligand (MC903) treatments are widely used and accepted models to study atopic like changes in mice [26][27][28][29][30]. In opposite, systemic treatments were shown to improve allergen-triggered eczema in a mouse model [31].…”

Section: Introductionmentioning

confidence: 99%

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Plasma Levels of Bioactive Vitamin D and A5 Ligands Positively Correlate with Clinical Atopic Dermatitis Markers

Lucas

Szklenar²,

Mihály

et al. 2022

Dermatology

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Background: Over the past decade, several controversial studies described a relationship between vitamin D and atopic diseases. Low plasma vitamin D levels or even vitamin D deficiency was associated with an increased incidence of atopic disease, postulating that a higher dietary intake of vitamin D may be a beneficial strategy against atopic diseases such as atopic dermatitis (AD). Objective: Our aim was to determine the relationship between plasma 25-hydroxyvitamin D3 (25(OH)D3) levels, the levels of the ligand of the vitamin D receptor (VDR) heterodimerization partner as well as the retinoid X receptor (RXR) and the active vitamin A5 derivative 9-cis-13,14-dihydroretinoic acid (9CDHRA) and AD severity. Methods/Results: Samples from AD patients (n = 20) and healthy volunteers (n = 20) were assessed. In our study, the frequently measured VDR ligand precursor 25(OH)D3 in addition to the VDR-ligand 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 9CDHRA displayed no different levels when compared with the plasma of AD patients and healthy volunteers. When performing further correlation studies focusing on AD patients, plasma 25(OH)D3 levels showed a negative correlation with eosinophils in blood (EOS) and SCORing Atopic Dermatitis (SCORAD) values, while 1,25(OH)2D3 and 9CDHRA levels correlated positively with plasma IgE, EOS, and SCORAD values. Conclusion: In consequence, the metabolic activation of vitamin D from 25(OH)D3 towards 1,25(OH)2D3 as well as the co-liganding of the RXR by 9CDHRA may be an important signalling mechanism, an important marker for AD development and severity as well as the basis for novel nutritional and pharmaceutical AD treatment options.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma Levels of Bioactive Vitamin D and A5 Ligands Positively Correlate with Clinical Atopic Dermatitis Markers

Lucas

Szklenar²,

Mihály

et al. 2022

Dermatology

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“…116 Furthermore, the induction of epidermal hyperproliferation in mouse skin by VDR antagonists occurs through the enhanced activation of RARγ mediated pathways (Figure 3F). 117…”

Section: The Interaction Between Nrsmentioning

confidence: 99%

Nuclear receptors for epidermal lipid barrier: Advances in mechanisms and applications

Yin,

Yan,

et al. 2024

Experimental Dermatology

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The skin plays an essential role in preventing the entry of external environmental threats and the loss of internal substances, depending on the epidermal permeability barrier. Nuclear receptors (NRs), present in various tissues and organs including full‐thickness skin, have been demonstrated to exert significant effects on the epidermal lipid barrier. Formation of the lipid lamellar membrane and the normal proliferation and differentiation of keratinocytes (KCs) are crucial for the development of the epidermal permeability barrier and is regulated by specific NRs such as PPAR, LXR, VDR, RAR/RXR, AHR, PXR and FXR. These receptors play a key role in regulating KC differentiation and the entire process of epidermal lipid synthesis, processing and secretion. Lipids derived from sebaceous glands are influenced by NRs as well and participate in regulation of the epidermal lipid barrier. Furthermore, intricate interplay exists between these receptors. Disturbance of barrier function leads to a range of diseases, including psoriasis, atopic dermatitis and acne. Targeting these NRs with agonists or antagonists modulate pathways involved in lipid synthesis and cell differentiation, suggesting potential therapeutic approaches for dermatosis associated with barrier damage. This review focuses on the regulatory role of NRs in the maintenance and processing of the epidermal lipid barrier through their effects on skin lipid synthesis and KC differentiation, providing novel insights for drug targets to facilitate precision medicine strategies.

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Impact of vitamin D supplementation as COVID-19 vaccine adjuvant on sperm parameters and sex hormones in men with idiopathic infertility: Two separate pre–post studies

Zarepoor,

Nazari,

Pourmasumi

2024

Clin Exp Reprod Med

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Objective: Vitamin D deficiency is a major problem for human health worldwide. The mechanisms of vitamin D in the male reproductive system are unknown. After coronavirus disease 2019 (COVID-19) vaccines were developed, doubts were raised about their possible effects on male fertility. Based on vitamin D’s function in the immune system, its potential role as an adjuvant for COVID-19 vaccines is intriguing. The aims of this study were to assess the effects of vitamin D first on sperm parameters and sex hormones, and then as an immune adjuvant on sperm parameters and sex hormones after study participants had received their second doses of COVID-19 vaccines.Methods: Phase 1 (before the COVID-19 pandemic) included 72 men with idiopathic infertility, and phase 2 had 64 participants who received two doses of COVID-19 vaccines. Both groups were instructed to take 50,000 IU of vitamin D twice monthly for 3 months. Sperm parameters and sex hormones were assessed pre- and post-supplementation.Results: Regular vitamin D intake for 3 months significantly increased the participants’ vitamin D levels (p=0.0001). Both phases showed a positive correlation between vitamin D intake and sperm parameters. Vaccination had no negative effects on sperm parameters and sex hormones. Vitamin D was associated with follicle-stimulating hormone (p=0.02) and testosterone (p=0.0001) in phase 2 after treatment. Conclusion: Our results support vitamin D supplementation as an immune adjunct to COVID-19 vaccination for improving sperm parameters and hormone levels. COVID-19 vaccination is not harmful for male fertility potential, and vitamin D is an effective factor for male fertility.

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Topical Vitamin D Receptor Antagonist/Partial-Agonist Treatment Induces Epidermal Hyperproliferation via RARγ Signaling Pathways

Cited by 3 publications

References 47 publications

Plasma Levels of Bioactive Vitamin D and A5 Ligands Positively Correlate with Clinical Atopic Dermatitis Markers

Plasma Levels of Bioactive Vitamin D and A5 Ligands Positively Correlate with Clinical Atopic Dermatitis Markers

Nuclear receptors for epidermal lipid barrier: Advances in mechanisms and applications

Impact of vitamin D supplementation as COVID-19 vaccine adjuvant on sperm parameters and sex hormones in men with idiopathic infertility: Two separate pre–post studies

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