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Vitamin D/VDR in the pathogenesis of intervertebral disc degeneration: Does autophagy play a role?
Lan, T, Shen, Z, Hu, Z, Yan, B
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112739
Abstract
To date, the underlying mechanisms involved intervertebral disc degeneration (IDD) remain unclear, which has hindered the development of molecular biological therapy for IDD. Autophagy is vital for intracellular quality control and metabolic balance in intervertebral disc cells. Hence, autophagy homeostasis is important. Emerging evidence has implicated vitamin D (VD) and the vitamin D receptor (VDR) in IDD progression because of their effects on different autophagy steps. However, the results of clinical trials in which VD supplementation was assessed as a treatment for IDD are controversial. Furthermore, experimental studies on the interplay between VD/VDR and autophagy are still in their infancy. In view of the significance of the crosstalk between VD/VDR and autophagy components, this review focuses on the latest research on VD/VDR modulation in autophagy and investigates the possible regulatory mechanisms. This article will deepen our understanding of the relationship between VD/VDR and autophagy and suggests novel strategies for IDD prevention and treatment.
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Gut instincts: vitamin D/vitamin D receptor and microbiome in neurodevelopment disorders.
Ogbu, D, Xia, E, Sun, J
Open biology. 2020;(7):200063
Abstract
The gut microbiome regulates a relationship with the brain known as the gut-microbiota-brain (GMB) axis. This interaction is influenced by immune cells, microbial metabolites and neurotransmitters. Recent findings show gut dysbiosis is prevalent in autism spectrum disorder (ASD) as well as attention deficit hyperactivity disorder (ADHD). There are previously established negative correlations among vitamin D, vitamin D receptor (VDR) levels and severity of ASD as well as ADHD. Both vitamin D and VDR are known to regulate homeostasis in the brain and the intestinal microbiome. This review summarizes the growing relationship between vitamin D/VDR signalling and the GMB axis in ASD and ADHD. We focus on current publications and summarize the progress of GMB in neurodevelopmental disorders, describe effects and mechanisms of vitamin D/VDR in regulating the microbiome and synoptically highlight the potential applications of targeting vitamin D/VDR signalling in neurodevelopment disorders.
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Mechanisms of action of vitamin D in colon cancer.
Ferrer-Mayorga, G, Larriba, MJ, Crespo, P, Muñoz, A
The Journal of steroid biochemistry and molecular biology. 2019;:1-6
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Abstract
Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC. Recently, our group has shown that calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts (CAFs). Accordingly, high VDR expression in tumor stromal fibroblasts is associated with longer survival of CRC patients. Moreover, many types of immune cells express VDR and are regulated by calcitriol, which probably contributes to its action against CRC. Given the role attributed to the intestinal microbiota in CRC and the finding that it is altered by vitamin D deficiency, an indirect antitumoral effect of calcitriol is also plausible at this level. In summary, calcitriol has an array of potential protective effects against CRC by acting on carcinoma cells, CAFs, immune cells and probably also the gut microbiota.
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Extra-Skeletal Effects of Vitamin D.
Marino, R, Misra, M
Nutrients. 2019;(7)
Abstract
The vitamin D receptor is expressed in multiple cells of the body (other than osteoblasts), including beta cells and cells involved in immune modulation (such as mononuclear cells, and activated T and B lymphocytes), and most organs in the body including the brain, heart, skin, gonads, prostate, breast, and gut. Consequently, the extra-skeletal impact of vitamin D deficiency has been an active area of research. While epidemiological and case-control studies have often suggested a link between vitamin D deficiency and conditions such as type 1 and type 2 diabetes, connective tissue disorders, inflammatory bowel disorders, chronic hepatitis, food allergies, asthma and respiratory infections, and cancer, interventional studies for the most part have failed to confirm a causative link. This review examines available evidence to date for the extra-skeletal effects of vitamin D deficiency, with a focus on randomized controlled trials and meta-analyses.
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Genetic Factors and Molecular Mechanisms of Vitamin D and Obesity Relationship.
Ruiz-Ojeda, FJ, Anguita-Ruiz, A, Leis, R, Aguilera, CM
Annals of nutrition & metabolism. 2018;(2):89-99
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Abstract
Vitamin D (vitD) deficiency is associated with a wide range of chronic diseases and conditions, including obesity, and with an increasing severity of metabolic dysregulation, such as insulin resistance, hyperlipidemia, liver disease, and hypertension, both in children and adults. However, the nature of the association between low vitD status and obesity remains unclear. This fact has motivated the scientific community to conduct genetic association analyses between 25-hydroxyvitamin D (25[OH]D)-related genes and obesity traits. In this line, the variation in the vitD receptor (VDR) gene represents the bulk of the findings. Specifically, polymorphisms in the VDR gene have been associated with obesity traits in some but not all, studies. Thus, results regarding this matter remain inconclusive. Other genes aside from VDR have also been investigated in relation to obesity-related traits. However, again, findings have been inconsistent. In general, results point to the fact that the DBP/GC gene could be an important protein-linking obesity and vitD status. On the other hand, several studies have attempted to determine the molecular mechanism of the relationship between 25(OH)-D levels and obesity. Some of these studies suggest that vitD, due to its fat-soluble characteristic, is retained by the adipose tissue and has the capacity to metabolize 25(OH)-D locally, and this can be altered during obesity. Additionally, vitD is capable of regulating the gene expression related to adipogenesis process, inflammation, oxidative stress, and metabolism in mature adipocytes. Therefore, the aim of the present review was to evaluate the association between obesity and vitD deficiency describing the main molecular mechanism of the relationship and the link with genetic factors. Key Messages: Low serum 25(OH)-D is positively associated with obesity or BMI in adults and children. Circulating vitD concentrations are, at least, partially determined by genetic factors. VitD plays an important role in the adipogenesis process and inflammation status in adipocytes and adipose tissue.
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Association of vitamin D receptor BsmI rs1544410 and ApaI rs7975232 polymorphisms with susceptibility to adolescent idiopathic scoliosis: A systematic review and meta-analysis.
Yin, X, Wang, H, Guo, J, Zhang, L, Zhang, Y, Li, L, Hou, S
Medicine. 2018;(2):e9627
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Abstract
BACKGROUND AIS is the most common spinal deformity disease, yet its etiology remains uncertain. Significant associations have been found between AIS risk and vitamin D receptor (VDR) gene polymorphisms; however, some of these results are controversial. The aim of this study was to determine whether VDR BsmI rs1544410 and ApaI rs7975232 polymorphisms are correlated with AIS. METHODS Databases, including PubMed, EMBASE, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Database, and the Wanfang Database, were systematically searched, and eligible case-control studies that explored the association of VDR (BsmI and ApaI) and the susceptibility to AIS were selected. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study population. RESULTS A total of 5 studies with 717 cases and 554 controls fulfilled the inclusion criteria after assessment by 2 reviewers. Generally, significant correlations were found between the BsmI polymorphism and AIS risk in overall populations and in Asian populations (overall population: B vs b: OR = 2.12, 95% CI = 1.21-3.75, P = .009; BB vs bb: OR = 3.38, 95% CI = 1.08-10.57, P = .036; Bb vs bb: OR = 2.50, 95% CI = 1.29-4.82, P = .006; BB/Bb vs bb: OR = 2.71, 95% CI = 1.31-5.63, P = .007; Asian population: B vs b: OR = 2.42, 95% CI = 1.27-4.61, P = .007; BB vs bb: OR = 4.09, 95% CI = 1.03-16.22, P = .045; Bb vs bb: OR = 2.94, 95% CI = 1.42-6.10, P = .004; BB/Bb vs bb: OR = 3.23, 95% CI = 1.42-7.35, P = .005). There was no significant association observed in Caucasian populations (all P > .05). With regard to the ApaI polymorphism, we found that it significantly decreased the risk of AIS (Aa vs AA: OR = 0.43, 95% CI = 0.24-0.77, P = .004; Aa/aa vs AA: OR = 0.52, 95% CI = 0.30-0.91, P = .023); however, we could not draw a definitive conclusion for Caucasian populations, as no studies have been conducted in this group to determine the role of the VDR ApaI polymorphism in AIS etiology and development. CONCLUSION VDR BsmI was significantly associated with AIS susceptibility in the overall and Asian populations, while the VDR ApaI polymorphism only played a key role in AIS etiology and development in Asian populations.
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[The impact of VDR gene polymorphisms on obesity, metabolic changes, bone mass disorders and neoplastic processes].
Wysoczańska-Klaczyńska, A, Ślęzak, A, Hetman, M, Barg, E
Pediatric endocrinology, diabetes, and metabolism. 2018;(2):96-105
Abstract
Vitamin D activity is controlled by its receptor (VDR) located in many cells of the body. The presence of VDR in numerous cellular pathways suggests its important role in the etiology and development of many diseases. Increased risk of obesity, metabolic disturbances, bone mass disturbances and neoplasia among certain VDR alleles has been proven. The importance of VDR in the etiopathology of obesity is associated with the occurrence of polymorphisms: Fok1, Bsm1, Apa1, Taq1. VDR expression in adipocytes plays a role in the regulation of energy metabolism and the induction of obesity. Vitamin D and VDR polymorphisms can participate in the development of many metabolic disorders. The VDR gene is one of the better researched genes among patients with type 1 diabetes. The action of vitamin D affects the proper functioning and development of the skeletal system. Vitamin D has an effect on bone remodeling through its receptor and its polymorphisms: Apa1, Bsm1, Taq1, Fok1 and Cdx2. The identification and diagnosis of VDR varieties gives the possibility of early detection of the risk of osteoporosis or individual predisposition to its development. There is a high variability in the results of individual VDR polymorphisms in relation to the occurrence of osteoporosis among various ethnic groups. The polymorphisms important in the neoplastic process include, among others, the polymorphism of Fok1, Bsm1, and Taq1. The association of VDR gene polymorphisms with the risk of breast cancer (Bsm1, Fok1), prostate cancer (Fok1) and malignant melanoma (Fok1) is indicated. The greatest importance in the prognosis is observed in patients with prostate cancer (F1), breast cancer (Bsm1, Taq1), malignant melanoma (Bsm1) and renal cell carcinoma (Taq1). It is important to identify, describe and correlate the occurrence of genetic polymorphisms of the VDR, which will allow early diagnosis or prevention of correlative entities correlated with them.
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Vitamin D receptor gene polymorphism, serum 25-hydroxyvitamin D levels, and risk of vitiligo: A meta-analysis.
Zhang, JZ, Wang, M, Ding, Y, Gao, F, Feng, YY, Yakeya, B, Wang, P, Wu, XJ, Hu, FX, Xian, J, et al
Medicine. 2018;(29):e11506
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Abstract
OBJECTIVES To explore the relationship among the vitamin D receptor (VDR) gene polymorphisms, serum 25-hydroxyvitamin D levels, and vitiligo. METHODS Databases including PubMed, Cochrane Library, Ovid, Web of Science, CNKI, SinoMed, and Wanfang Data were systematically searched. The association was assessed using odds ratios (ORs), standard mean difference (SMD), and 95% confidence intervals (CIs). The statistical tests were performed using Review Manager 5.3.3. RESULTS We identified a total of 17 studies. The relationship between VDR gene polymorphisms (BsmI, ApaI, TaqI, and FokI), serum 25 (OH)D levels, and incidence of vitiligo was investigated. The results of this meta-analysis showed that the dominant genetic model (CC+AC vs AA, P = .007, OR = 1.41, 95% CI = 1.10-1.80), recessive genetic model (CC vs AC+AA, P = .01, OR = 4.10, 95% CI = 1.36-12.35), and allelic contrast model (C vs A, P = .005, OR = 1.87, 95% CI = 1.21-2.90) of VDR Apal locus increased the risk of vitiligo, and BsmI, TaqI, and FokI loci and the risk of vitiligo have no obvious correlation. Serum 25 (OH)D deficiency was positively associated with the incidence of vitiligo (P < .0001, SMD = -0.94, 95% CI = -1.39, -0.48). CONCLUSION This meta-analysis revealed that VDR Apal polymorphism increased the susceptibility risk of vitiligo, and there is a positive correlation between serum 25 (OH)D deficiency and the incidence of vitiligo.
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Dietary vitamin D, vitamin D receptor, and microbiome.
Sun, J
Current opinion in clinical nutrition and metabolic care. 2018;(6):471-474
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PURPOSE OF REVIEW The current review is to summarize the recent progress of vitamin D/vitamin D receptor (VDR) and microbiome in intestinal homeostasis, airway function, and other organs. RECENT FINDINGS Microbiome is considered as a newly discovered human organ. It is critical in the synthesis of vitamins and harvest of otherwise inaccessible nutrients, metabolism of xenobiotics, body fat storage, renewal of gut epithelial cells, and mature of immune system. Vitamin D and VDR are known to regulate microbiome in health and disease. We will focus on the recent findings published in 12-18 months and discuss the vitamin D supplement and its effects on microbiome, intestinal homeostasis, airway function, and metabolism. We will emphasize the tissue specificity and genetic factor of VDR and microbiome. SUMMARY The findings in dietary vitamin D, VDR, and microbiome with personalized genetic information will be implicated for optimal prevention and treatment of chronic diseases.
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Vitamin D and Autoimmune Diseases: Is Vitamin D Receptor (VDR) Polymorphism the Culprit?
Bizzaro, G, Antico, A, Fortunato, A, Bizzaro, N
The Israel Medical Association journal : IMAJ. 2017;(7):438-443
Abstract
Vitamin D deficiency is becoming an increasing problem worldwide. It should not be underestimated, not only due to the well-known consequences vitamin D deficiency has on bone health, but primarily because recent studies have shown how the biologically active form of vitamin D - 1,25(OH)2D - is involved in many biological processes, including immune system modulation. Moreover, the presence of a vitamin D receptor was discovered in almost all immune cells and some of its polymorphisms were found to be associated with increased incidence of autoimmune diseases. This finding led to a proposed link between vitamin D deficiency and autoimmune diseases. Patients affected by various autoimmune diseases showed low levels of vitamin D. However, it is not always clear whether vitamin D deficiency is the cause or rather a consequence of the disease. Limitations of the studies, such as the small number of patients, heterogeneity of selected groups, environmental conditions, methods used to measure vitamin D serum concentration and other confounding factors do not lead to unequivocal results to demonstrate a direct link between low vitamin D levels and autoimmune disease. Therefore, randomized trials are needed to clarify conflicting results.