Vitamin D and the intestine: Review and update

Christakos, Sylvia; Li, Shanshan; Cruz, Jessica De La; Shroyer, Noah F.; Criss, Zachary K.; Verzi, Michael P.; Fleet, James C.

doi:10.1016/j.jsbmb.2019.105501

Cited by 47 publications

(38 citation statements)

References 58 publications

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“…1,25(OH) 2 D 3 action in vivo has been explored at different mechanistic levels in intestinal epithelia and in kidney cortex (enriched in proximal tubules). In intestinal epithelial cells isolated from mice pre-injected with 1,25(OH) 2 D 3 , the VDR is bound to multiple genes across the mouse genome; its binding is enhanced by prior treatment with 1,25(OH) 2 D 3 [100][101][102]. More recent studies have revealed differences in VDR binding in enterocytes vs. crypt cells, suggesting differential roles for vitamin D in these two cells [101,102].…”

Section: Recent Work At the Frontier For Enhancing Vitamin D Analogue Sar Potentialmentioning

confidence: 99%

New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues

Pike

Meyer

2021

IJMS

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Recent studies of transcription have revealed an advanced set of overarching principles that govern vitamin D action on a genome-wide scale. These tenets of vitamin D transcription have emerged as a result of the application of now well-established techniques of chromatin immunoprecipitation coupled to next-generation DNA sequencing that have now been linked directly to CRISPR-Cas9 genomic editing in culture cells and in mouse tissues in vivo. Accordingly, these techniques have established that the vitamin D hormone modulates sets of cell-type specific genes via an initial action that involves rapid binding of the VDR–ligand complex to multiple enhancer elements at open chromatin sites that drive the expression of individual genes. Importantly, a sequential set of downstream events follows this initial binding that results in rapid histone acetylation at these sites, the recruitment of additional histone modifiers across the gene locus, and in many cases, the appearance of H3K36me3 and RNA polymerase II across gene bodies. The measured recruitment of these factors and/or activities and their presence at specific regions in the gene locus correlate with the emerging presence of cognate transcripts, thereby highlighting sequential molecular events that occur during activation of most genes both in vitro and in vivo. These features provide a novel approach to the study of vitamin D analogs and their actions in vivo and suggest that they can be used for synthetic compound evaluation and to select for novel tissue- and gene-specific features. This may be particularly useful for ligand activation of nuclear receptors given the targeting of these factors directly to genetic sites in the nucleus.

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Section: Recent Work At the Frontier For Enhancing Vitamin D Analogue Sar Potentialmentioning

confidence: 99%

New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues

Pike

Meyer

2021

IJMS

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“…In line with its physiological role in the intestine, promoting the absorption of calcium and phosphate, the intestinal epithelium barrier function and xenobiotic metabolism, 1,25(OH) 2 D 3 induces the differentiation of normal colon epithelial cells through the upregulation of many epithelial enzymes and markers and through maintaining the morphology typical of the epithelial differentiated phenotype [ 14 , 15 ]. Concordantly, in colon carcinoma cells 1,25(OH) 2 D 3 induces a change in morphology that increases cell–cell adhesion and cell flattening ( Figure 1 a), which is paralleled by a decrease in proliferation.…”

Section: Effects Of 125(oh) 2 D 3 mentioning

confidence: 99%

Vitamin D Effects on Cell Differentiation and Stemness in Cancer

Fernández‐Barral

Bustamante-Madrid

Ferrer-Mayorga

et al. 2020

Cancers

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Vitamin D3 is the precursor of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), a pleiotropic hormone that is a major regulator of the human genome. 1,25(OH)2D3 modulates the phenotype and physiology of many cell types by controlling the expression of hundreds of genes in a tissue- and cell-specific fashion. Vitamin D deficiency is common among cancer patients and numerous studies have reported that 1,25(OH)2D3 promotes the differentiation of a wide panel of cultured carcinoma cells, frequently associated with a reduction in cell proliferation and survival. A major mechanism of this action is inhibition of the epithelial–mesenchymal transition, which in turn is largely based on antagonism of the Wnt/β-catenin, TGF-β and EGF signaling pathways. In addition, 1,25(OH)2D3 controls the gene expression profile and phenotype of cancer-associated fibroblasts (CAFs), which are important players in the tumorigenic process. Moreover, recent data suggest a regulatory role of 1,25(OH)2D3 in the biology of normal and cancer stem cells (CSCs). Here, we revise the current knowledge of the molecular and genetic basis of the regulation by 1,25(OH)2D3 of the differentiation and stemness of human carcinoma cells, CAFs and CSCs. These effects support a homeostatic non-cytotoxic anticancer action of 1,25(OH)2D3 based on reprogramming of the phenotype of several cell types.

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“…Dr. Wasserman's research on the identification, induction by vitamin D, and function of the intestinal and renal calcium binding proteins (calbindin D9k and D28k in mammals, respectively) served as a foundation for the facilitated diffusion model of transepithelial calcium transport. After her tribute, Dr. Christakos continued to give an invited talk that described new research on vitamin D signaling in the intestine [21]. He talk began with a review of her recent publication on the role of signaling through the VDR in the distal intestine.…”

Section: Overviewmentioning

confidence: 99%