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Vitamin D and Vitamin D Binding Protein in Health and Disease 3.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: 20 December 2024 | Viewed by 6283

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Department of Internal Medicine, Nephrology Division, Ghent University Hospital, 9000 Ghent, Belgium
Interests: biochemistry; biomarkers; hypertension; cardiovascular disease; kidney disease
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Special Issue Information

Dear Colleagues,

Vitamin D functions in the human body through both an endocrine and an autocrine mechanism. Nearly all circulating vitamin D (~85–90%) circulates bound to vitamin D-binding protein (DBP), with a smaller proportion bound to albumin, leaving <5% circulating freely. DBP is a multifunctional protein that has attracted increasing interest in recent years. DBP may also play roles beyond vitamin D binding, with potential roles in the immune system and elsewhere. The consequences of low 25(OH)D status include increased risk of various chronic diseases, ranging from hypertension to diabetes to cancer and infections. Also, the DBP polymorphism with more than 120 variants has been linked to several diseases. Despite the enormous progress in the deciphering of the structure of DBP and its function, there remains an impressive list of major research questions. In this special issue, we welcome original papers and review articles, which focus on the role of vitamin and DBP in health and disease.

More published papers can be found in the closed special issue:
Vitamin D and Vitamin D Binding Protein in Health and Disease;
Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0.

Prof. Dr. Marijn Speeckaert
Guest Editor

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Keywords

  • vitamin D
  • vitamin D binding protein (gc-globulin)
  • vitamin D receptor
  • vitamin D deficiency
  • immunomodulation
  • chronic inflammatory diseases
  • osteoporosis
  • vitamin D deficiency

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Published Papers (4 papers)

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Research

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14 pages, 805 KiB  
Article
The Effect of Phototherapy on Systemic Inflammation Measured with Serum Vitamin D-Binding Protein and hsCRP in Patients with Inflammatory Skin Disease
by Andrea Elmelid, Maria Siekkeri Vandikas, Martin Gillstedt, Mikael Alsterholm and Amra Osmancevic
Int. J. Mol. Sci. 2024, 25(16), 8632; https://doi.org/10.3390/ijms25168632 - 8 Aug 2024
Cited by 1 | Viewed by 929
Abstract
Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) [...] Read more.
Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) acts as the major transporter of vitamin D in the circulation, and DBP concentration defines the free 25(OH)D levels. DBP levels are elevated in various inflammatory conditions, including psoriasis. Narrowband-ultraviolet B (NB-UVB) is the most widely used phototherapy and is an established first-line treatment for psoriasis and atopic dermatitis (AD), often used before proceeding to systemic treatment. The aim of this study was to investigate the influence of NB-UVB phototherapy on DBP and high-sensitivity C-reactive protein (hsCRP) levels, as markers of systemic inflammation, in inflammatory skin disease. Thirty adults (psoriasis (n = 20) and AD (n = 10)) were treated with NB-UVB. Serum DBP, hsCRP, total and free 25(OH)D, and 1,25-dihydroxy vitamin D (1,25(OH)2D) were measured before and after NB-UVB. Disease severity was assessed with Psoriasis Area and Severity Index (PASI), SCORing Atopic Dermatitis (SCORAD), and Visual Analogue Scale (VAS). DBP decreased in psoriasis patients and varied with no clear trend in AD patients. HsCRP decreased in both groups, but this did not reach statistical significance. PASI, SCORAD, and VAS improved, and vitamin D levels increased after NB-UVB. Sub-analysis indicated a better response to NB-UVB for patients with vitamin D deficiency and insufficiency compared to vitamin D-sufficient patients. The decrease in DBP after NB-UVB in psoriasis patients suggests a potential systemic anti-inflammatory effect of phototherapy. Measurement of vitamin D levels may potentially serve as a tool to identify patients who would derive the greatest benefit from NB-UVB phototherapy. Full article
(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 3.0)
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37 pages, 8919 KiB  
Article
The Molecular Aspects of Functional Activity of Macrophage-Activating Factor GcMAF
by Svetlana S. Kirikovich, Evgeniy V. Levites, Anastasia S. Proskurina, Genrikh S. Ritter, Sergey E. Peltek, Asya R. Vasilieva, Vera S. Ruzanova, Evgeniya V. Dolgova, Sofya G. Oshihmina, Alexandr V. Sysoev, Danil I. Koleno, Elena D. Danilenko, Oleg S. Taranov, Alexandr A. Ostanin, Elena R. Chernykh, Nikolay A. Kolchanov and Sergey S. Bogachev
Int. J. Mol. Sci. 2023, 24(24), 17396; https://doi.org/10.3390/ijms242417396 - 12 Dec 2023
Cited by 3 | Viewed by 1622
Abstract
Group-specific component macrophage-activating factor (GcMAF) is the vitamin D3-binding protein (DBP) deglycosylated at Thr420. The protein is believed to exhibit a wide range of therapeutic properties associated with the activation of macrophagal immunity. An original method for GcMAF production, [...] Read more.
Group-specific component macrophage-activating factor (GcMAF) is the vitamin D3-binding protein (DBP) deglycosylated at Thr420. The protein is believed to exhibit a wide range of therapeutic properties associated with the activation of macrophagal immunity. An original method for GcMAF production, DBP conversion to GcMAF, and the analysis of the activating potency of GcMAF was developed in this study. Data unveiling the molecular causes of macrophage activation were obtained. GcMAF was found to interact with three CLEC10A derivatives having molecular weights of 29 kDa, 63 kDa, and 65 kDa. GcMAF interacts with high-molecular-weight derivatives via Ca2+-dependent receptor engagement. Binding to the 65 kDa or 63 kDa derivative determines the pro- and anti-inflammatory direction of cytokine mRNA expression: 65 kDa—pro-inflammatory (TNF-α, IL-1β) and 63 kDa—anti-inflammatory (TGF-β, IL-10). No Ca2+ ions are required for the interaction with the canonical 29 kDa CLEC10A. Both forms, DBP protein and GcMAF, bind to the 29 kDa CLEC10A. This interaction is characterized by the stochastic mRNA synthesis of the analyzed cytokines. Ex vivo experiments have demonstrated that when there is an excess of GcMAF ligand, CLEC10A forms aggregate, and the mRNA synthesis of analyzed cytokines is inhibited. A schematic diagram of the presumable mechanism of interaction between the CLEC10A derivatives and GcMAF is provided. The principles and elements of standardizing the GcMAF preparation are elaborated. Full article
(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 3.0)
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Review

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17 pages, 698 KiB  
Review
Investigating Vitamin D-Binding Protein’s Role in Childhood Health and Development
by Charlotte Delrue, Reinhart Speeckaert, Joris R. Delanghe, Agnieszka Prytuła and Marijn M. Speeckaert
Int. J. Mol. Sci. 2024, 25(11), 6272; https://doi.org/10.3390/ijms25116272 - 6 Jun 2024
Viewed by 1241
Abstract
Vitamin D-binding protein (DBP), also known as Gc-globulin, is a protein that affects several physiological processes, including the transport and regulation of vitamin D metabolites. Genetic polymorphisms in the DBP gene have a significant impact on vitamin D levels and may have implications [...] Read more.
Vitamin D-binding protein (DBP), also known as Gc-globulin, is a protein that affects several physiological processes, including the transport and regulation of vitamin D metabolites. Genetic polymorphisms in the DBP gene have a significant impact on vitamin D levels and may have implications for disease risk. DBP polymorphisms are linked to differential immune responses, which could influence the onset of juvenile diseases. This narrative review examines the various roles of DBP, with a focus on bone health, immunological regulation, and lipid metabolism in children. Chronic disorders affected by DBP polymorphisms include bone abnormalities, autoimmune diseases, cardiovascular issues, childhood asthma, allergies, cystic fibrosis, acute liver failure, celiac disease, inflammatory bowel disease, and chronic kidney disease. Future research should focus on identifying the processes that underpin the many roles that DBP plays and developing customized therapeutics to improve health outcomes in the juvenile population. Full article
(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 3.0)
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14 pages, 1780 KiB  
Review
Role of Calcitriol and Vitamin D Receptor (VDR) Gene Polymorphisms in Alzheimer’s Disease
by Soon Pyo Jeong, Niti Sharma and Seong Soo A. An
Int. J. Mol. Sci. 2024, 25(9), 4806; https://doi.org/10.3390/ijms25094806 - 28 Apr 2024
Cited by 1 | Viewed by 1696
Abstract
Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) buildup and neuronal degeneration. An association between low serum vitamin D levels and an increased risk of AD has been reported in several epidemiological studies. Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D, [...] Read more.
Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) buildup and neuronal degeneration. An association between low serum vitamin D levels and an increased risk of AD has been reported in several epidemiological studies. Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D, and is generated in the kidney and many other tissues/organs, including the brain. It is a steroid hormone that regulates important functions like calcium/phosphorous levels, bone mineralization, and immunomodulation, indicating its broader systemic significance. In addition, calcitriol confers neuroprotection by mitigating oxidative stress and neuroinflammation, promoting the clearance of Aβ, myelin formation, neurogenesis, neurotransmission, and autophagy. The receptors to which calcitriol binds (vitamin D receptors; VDRs) to exert its effects are distributed over many organs and tissues, representing other significant roles of calcitriol beyond sustaining bone health. The biological effects of calcitriol are manifested through genomic (classical) and non-genomic actions through different pathways. The first is a slow genomic effect involving nuclear VDR directly affecting gene transcription. The association of AD with VDR gene polymorphisms relies on the changes in vitamin D consumption, which lowers VDR expression, protein stability, and binding affinity. It leads to the altered expression of genes involved in the neuroprotective effects of calcitriol. This review summarizes the neuroprotective mechanism of calcitriol and the role of VDR polymorphisms in AD, and might help develop potential therapeutic strategies and markers for AD in the future. Full article
(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 3.0)
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