New aspects of vitamin D metabolism and action — addressing the skin as source and target

Bikle, Daniel; Christakos, Sylvia

doi:10.1038/s41574-019-0312-5

Cited by 232 publications

(223 citation statements)

References 284 publications

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“…2 Vitamin D is a secosteroid hormone, derived like cortisol and sex hormones from cholesterol, so not surprisingly it has a broad range of actions reflecting the several hundred or more genes that are vitamin D responsive. 3,4 Thrombosis is another aspect of severe COVID-19 illness where vitamin D may be very important, as previously highlighted by Tian and Rong. 5 The lupus anti-coagulant abnormality, characterised by prolonged activated partial thromboplastin time, has recently been reported in COVID-19.…”

Section: Editorsmentioning

confidence: 89%

Letter: low population mortality from COVID‐19 in countries south of latitude 35° North supports vitamin D as a factor determining severity. Authors’ reply

Rhodes

Subramanian

Laird³

et al. 2020

Aliment Pharmacol Ther

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Section: Editorsmentioning

confidence: 89%

Letter: low population mortality from COVID‐19 in countries south of latitude 35° North supports vitamin D as a factor determining severity. Authors’ reply

Rhodes

Subramanian

Laird³

et al. 2020

Aliment Pharmacol Ther

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“…In this review, the gut-skin axis is the main target of discussion, thus skin-specific cells, such as epidermal keratinocytes and dermal fibroblasts, are not discussed. The nuclear receptors such as RARs, VDR, and RORs are expressed not only in immune cells, but also in epidermal keratinocytes [26], making the epidermal keratinocytes another target of immune regulation. Skin has its own microbiome, through influencing the homeostasis of epidermis, it regulates the immune status of the whole body.…”

Section: Discussionmentioning

confidence: 99%

“…Ultraviolet (UV) B and antimicrobial peptides, such as cathelicidin and S100 proteins, are inducers of active vitamin D3 production in epidermis. Active vitamin D3 systemically distribute through blood flow binding to vitamin D binding protein (DBP), enter target cells through binding to heat shock protein (HSP) 70 in cytoplasm, and finally transported to the nucleus binding to VDR [26]. VDR binds to its binding site in enhancer regions of Foxp3 gene, resulting in induction and stabilization of Foxp3 expression.…”

Section: Regulatory T Cellsmentioning

confidence: 99%

Recent Advances in Psoriasis Research; the Clue to Mysterious Relation to Gut Microbiome

Komine

2020

IJMS

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Psoriasis is a chronic inflammatory cutaneous disease, characterized by activated plasmacytoid dendritic cells, myeloid dendritic cells, Th17 cells, and hyperproliferating keratinocytes. Recent studies revealed skin-resident cells have pivotal roles in developing psoriatic skin lesions. The balance in effector T cells and regulatory T cells is disturbed, leading Foxp3-positive regulatory T cells to produce proinflammatory IL-17. Not only acquired but also innate immunity is important in psoriasis pathogenesis, especially in triggering the disease. Group 3 innate lymphoid cell are considered one of IL-17-producing cells in psoriasis. Short chain fatty acids produced by gut microbiota stabilize expression of Foxp3 in regulatory T cells, thereby stabilizing their function. The composition of gut microbiota influences the systemic inflammatory status, and associations been shown with diabetes mellitus, cardiovascular diseases, psychomotor diseases, and other systemic inflammatory disorders. Psoriasis has been shown to frequently comorbid with diabetes mellitus, cardiovascular diseases, psychomotor disease and obesity, and recent report suggested the similar abnormality in gut microbiota as the above comorbid diseases. However, the precise mechanism and relation between psoriasis pathogenesis and gut microbiota needs further investigation. This review introduces the recent advances in psoriasis research and tries to provide clues to solve the mysterious relation of psoriasis and gut microbiota.

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“…The amount of 7-DHC substrate available for the vitamin D 3 production is indirectly controlled by the activity of 7-dehydrocholesterol reductase (DHCR7), an enzyme involved in the last step of cholesterol synthesis, which, in the case of the skin, competes with the vitamin D production since both pathways require the same precursor [ 15 ]. UV light intensity and the type of skin pigmentation also regulate the production of pre-vitamin D 3 and, in turn, of vitamin D 3 [ 16 ].…”

Section: Vitamin D: State Of the Artmentioning

confidence: 99%

“…In the presence of low vitamin D status, PTH secretion—mediated by the parathyroid gland ( Figure 2 )—increases and promotes the activity of CYP27B1, leading to an enhanced conversion of 25(OH)D in 1,25(OH) 2 D [ 50 , 51 , 52 , 53 , 54 ]. In turn, circulating 1.25(OH) 2 D promotes the CYP24A1 activity while suppressing the CYP27B1 one; it also enhances the intestinal absorption of both calcium [ 55 ] and phosphate [ 15 , 47 ] and in parallel reduces the serum PTH levels by a negative feedback [ 56 , 57 ].…”

Section: Vitamin D: State Of the Artmentioning

confidence: 99%

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

Riccardi

Perrone

Napolitano

et al. 2020

Cancers

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Vitamin D is a fat-soluble steroid hormone playing a pivotal role in calcium and phosphate homeostasis as well as in bone health. Vitamin D levels are not exclusively dependent on food intake. Indeed, the endogenous production—occurring in the skin and dependent on sun exposure—contributes to the majority amount of vitamin D present in the body. Since vitamin D receptors (VDRs) are ubiquitous and drive the expression of hundreds of genes, the interest in vitamin D has tremendously grown and its role in different diseases has been extensively studied. Several investigations indicated that vitamin D action extends far beyond bone health and calcium metabolism, showing broad effects on a variety of critical illnesses, including cancer, infections, cardiovascular and autoimmune diseases. Epidemiological studies indicated that low circulating vitamin D levels inversely correlate with cutaneous manifestations and bone abnormalities, clinical hallmarks of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumour predisposition syndrome causing significant pain and morbidity, for which limited treatment options are available. In this context, vitamin D or its analogues have been used to treat both skin and bone lesions in NF1 patients, alone or combined with other therapeutic agents. Here we provide an overview of vitamin D, its characteristic nutritional properties relevant for health benefits and its role in NF1 disorder. We focus on preclinical and clinical studies that demonstrated the clinical correlation between vitamin D status and NF1 disease, thus providing important insights into disease pathogenesis and new opportunities for targeted therapy.

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New aspects of vitamin D metabolism and action — addressing the skin as source and target

Cited by 232 publications

References 284 publications

Letter: low population mortality from COVID‐19 in countries south of latitude 35° North supports vitamin D as a factor determining severity. Authors’ reply

Letter: low population mortality from COVID‐19 in countries south of latitude 35° North supports vitamin D as a factor determining severity. Authors’ reply

Recent Advances in Psoriasis Research; the Clue to Mysterious Relation to Gut Microbiome

Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

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