0
selected
-
1.
Vitamin D in trichology: a comprehensive review of the role of vitamin D and its receptor in hair and scalp disorders.
Damiani, G, Conic, R, Orlando, G, Zampetti, A, Marinello, E, Piai, M, Linder, MD
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia. 2020;(2):190-197
Abstract
Vitamin D plays an important role in maintaining the homeostasis of various biological systems. Beside its well-known function in calcium and phosphate metabolism, it plays a major role in pathophysiology of skin and adnexa. Indeed, vitamin D, through its receptor (VDR), decreases keratinocyte proliferation, improves their differentiation and modulates both cutaneous innate (antimicrobial activity and antigen presentation) and adaptative immunity (T and B lymphocyte function). The maintenance of normal hair is dependant on the integrity of the dermis, epidermis and hair cycles. Beside its effect on epidermal differentiation, VDR plays a vital role in preserving the hair follicle integrity. While the relevance of VDR has been fully elucidated, the real value of vitamin D in the hair follicle cycle still remains uncertain. To date, results in literature remain contradicting and far from definitive; still, the role of vitamin D in the various forms of human alopecia is likely to be significant. The aim of this article is to review evidence about the role of vitamin D and its receptor in trichology, with a focus on scarring and non-scarring alopecia and in particular on the potential therapeutic use of Vitamin D for hair and scalp disorders.
-
2.
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.
-
3.
The Vitamin D Receptor as Tumor Suppressor in Skin.
Bikle, DD
Advances in experimental medicine and biology. 2020;:285-306
Abstract
Cutaneous malignancies including melanomas and keratinocyte carcinomas (KC) are the most common types of cancer, occurring at a rate of over one million per year in the United States. KC, which include both basal cell carcinomas and squamous cell carcinomas, are substantially more common than melanomas and form the subject of this chapter. Ultraviolet radiation (UVR), both UVB and UVA, as occurs with sunlight exposure is generally regarded as causal for these malignancies, but UVB is also required for vitamin D synthesis in the skin. Keratinocytes are the major cell in the epidermis. These cells not only produce vitamin D but contain the enzymatic machinery to metabolize vitamin D to its active metabolite, 1,25(OH)2D, and express the receptor for this metabolite, the vitamin D receptor (VDR). This allows the cell to respond to the 1,25(OH)2D that it produces. Based on our own data and that reported in the literature, we conclude that vitamin D signaling in the skin suppresses UVR-induced epidermal tumor formation. In this chapter we focus on four mechanisms by which vitamin D signaling suppresses tumor formation. They are inhibition of proliferation/stimulation of differentiation with discussion of the roles of hedgehog, Wnt/β-catenin, and hyaluronan/CD44 pathways in mediating vitamin D regulation of proliferation/differentiation, regulation of the balance between oncogenic and tumor suppressor long noncoding RNAs, immune regulation, and promotion of DNA damage repair (DDR).
-
4.
Roles of Vitamin D in Reproductive Systems and Assisted Reproductive Technology.
Chen, Y, Zhi, X
Endocrinology. 2020;(4)
Abstract
Vitamin D, an essential steroid hormone in the human body, plays an important role in not only the regulation of calcium and phosphorus metabolism, but also in various physiological processes, such as cell differentiation and apoptosis, inflammation, and insulin resistance. Vitamin D receptors are widely distributed in male and female reproductive systems, suggesting that vitamin D is essential for fertility. Because vitamin D deficiency is highly prevalent around the world, this review aims to discuss the potential functions of vitamin D in male and female reproductive systems and the associations between vitamin D and assisted reproductive technology (ART) outcomes. Vitamin D is involved in many physiological reproductive processes, including steroidogenesis, spermatogenesis, and acrosome reaction. It is correlated with sperm quality, ovarian reserve, polycystic ovarian syndrome, and endometriosis, among others. Controversial clinical findings on vitamin D levels and ART outcomes were revealed in this review, and demonstrations of efficacy for human fertility in randomized controlled trials of vitamin D supplementation are notably lacking. Thus, further studies are highly required involving molecular mechanisms among different species and human populations, as well as randomized controlled trials.
-
5.
Vitamin D: A Micronutrient Regulating Genes.
Carlberg, C
Current pharmaceutical design. 2019;(15):1740-1746
Abstract
BACKGROUND At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the transcription factor vitamin D receptor (VDR). METHODS This review discusses the biological effects of micronutrient vitamin D ranging from calcium homeostasis and bone formation to the modulation of innate and adaptive immunity. RESULTS Since normal human diet is sufficient in vitamin D, the need for efficient vitamin D3 synthesis in the skin acts as an evolutionary driver for its lightening during the migration out of Africa towards North. Via activating the VDR, vitamin D has direct effects on the epigenome and the expression of more than 1000 genes in most human tissues and cell types. CONCLUSIONS The pleiotropic action of vitamin D in health and disease prevention is explained through complex gene regulatory events of the transcription factor VDR.
-
6.
Molecular basis of vitamin D action in neurodegeneration: the story of a team perspective.
Gezen-Ak, D, Dursun, E
Hormones (Athens, Greece). 2019;(1):17-21
Abstract
Vitamin D, a secosteroid hormone, has, over the years, mainly been known for its classic role in the maintenance of calcium homeostasis of the human body. However, there is increasing understanding that vitamin D contributes to the regulation of Ca2+ homeostasis, especially via voltage-gated calcium channels, in another major organ that uses calcium, the brain. Almost 30 years ago, the role of dysregulation in the aging brain and in Alzheimer's disease (AD) gave rise to the Ca2+ hypothesis of brain aging and dementia. We thus made calcium homeostasis the starting point of our studies, proposing the notion that the consequences of long-term deficiency and/or inefficient utilization of vitamin D may cause the disruption of calcium homeostasis in neurons, this creating a vulnerability of neurons to aging and neurodegeneration. In this mini-review, we aim to describe the potential of vitamin D (cholecalciferol) as a neurosteroid based on our findings and conclusions.
-
7.
Molecular evidence of role of vitamin D deficiency in various extraskeletal diseases.
Zendehdel, A, Arefi, M
Journal of cellular biochemistry. 2019;(6):8829-8840
Abstract
BACKGROUND Role of vitamin D is not only limited to skeletal system but various other systems of the body, such as immune system, endocrine system, and cardiopulmonary system. MATERIALS AND METHODS It is supported by the confirmations of systems-wide expression of vitamin D receptor (VDR), endocrinal effect of calcitriol, and its role in immune responses. RESULTS Expression of VDR in various systems, immunoregulatory and hormonal response of vitamin D and deficiency of vitamin D may establish various pathologies in the body. CONCLUSION This review provides molecular evidence of relation of vitamin D with extra skeletal.
-
8.
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
-
-
Free full text
-
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.
-
9.
The Significance of Vitamin D Status in Breast Cancer: A State of the Science Review.
McNamara, M, Rosenberger, KD
Journal of midwifery & women's health. 2019;(3):276-288
Abstract
The potential role of vitamin D in the development of breast cancer has been the subject of considerable interest. Laboratory and genetic studies demonstrate promising anticarcinogenic effects of vitamin D. However, inconsistencies persist in results of human studies that have assessed vitamin D supplementation for the prevention of primary and secondary cancers. Despite these discrepancies, screening for vitamin D deficiency and vitamin D supplementation have increased dramatically in the past decade. No official institutional guidelines recommend vitamin D supplementation for cancer prevention, and yet these newly adopted practice norms have outpaced rigorous scientific study. Higher circulating levels of vitamin D [25-hydroxyvitamin D, or 25(OH)D] appear to be associated with reduced risk and improved survivorship of certain malignancies. However, the association has not been found for all cancers. This state of the science review examines the association between vitamin D supplementation, circulating 25(OH)D level, vitamin D receptor polymorphisms, and the risk and mortality of breast cancer. The review addresses the role of supplementation and optimal 25(OH)D levels.
-
10.
Machine learning approaches infer vitamin D signaling: Critical impact of vitamin D receptor binding within topologically associated domains.
Carlberg, C, Neme, A
The Journal of steroid biochemistry and molecular biology. 2019;:103-109
Abstract
The vitamin D-modulated transcriptome of highly responsive human cells, such as THP-1 monocytes, comprises more than 500 genes, half of which are primary targets. Recently, we proposed a chromatin model of vitamin D signaling demonstrating that nearly all vitamin D target genes are located within vitamin D-modulated topologically associated domains (TADs). This model is based on genome-wide binding patterns of the vitamin D receptor (VDR), the pioneer transcription factor PU.1, the chromatin organizer CTCF and histone markers of active promoter regions (H3K4me3) and active chromatin (H3K27ac). In addition, time-dependent data on accessible chromatin and mRNA expression are implemented. For the interrogation and in deep inspection of these high-dimensional datasets unsupervised and supervised machine learning algorithms were applied. Unsupervised methods, such as the vector quantization tool K-means and the dimensionality reduction algorithm self-organizing map, generated descriptions of how attributes, such as VDR binding and chromatin accessibility, affect each other as a function of time and/or co-localization within the same genomic region. Supervised algorithms, such as random forests, allowed the data to be classified into pre-existing categories like persistent (i.e. constant) and time-dependent (i.e. transient) VDR binding sites. The relative amounts of these VDR categories in TADs showed to be the main discriminator for sorting the latter into five classes carrying vitamin D target genes involved in distinct biological processes. In conclusion, via the application of machine learning methods we identified the spatio-temporal VDR binding pattern in TADs as the most critical attribute for specific regulation of vitamin D target genes and the segregation of vitamin D's physiologic function.