Project description:In humans, vitamin D3 is a secosteroid, a prohormonal precursor of biologically active hydroxyforms. Vitamin D3 is related to periodontitis. The third American Health and Nutrition Survey found that plasma 25(OH)D3 levels are negatively correlated with attachment loss in people aged >50 years. The relationship between vitamin D3 and periodontitis remains to be investigated. We sent human gingival fibroblasts treated by vitamin D3 for transcriptome sequencing.
Project description:Total RNAs extracted from skin tissues of wild-type C57BL/6 or K5-Cre;VDR f/f mice stimulated by Oxarol and their mRNA expression profiles were analyzed by RNA-sequencing
Project description:Vitamin D insufficiency may exacerbate non-specific inflammation observed in older adults. Here, we tested the hypothesis that an inflammatory gene signature present in old skin following saline injection (as model for non-specific needle injury) normalizes after oral vitamin D3 supplementation. To define the saline-induced signature, we compared gene expression in skin biopsies taken six hours after saline injection in old adults (≥65 years) to biopsies from unmanipulated skin. We then assessed signature expression in saline-injected skin of old and young adults (<40 years), and in paired samples of old adults before and after oral vitamin D3 supplementation (6400 IU/day for 14 weeks), where median serum 25-hydroxyvitamin D increased from 43 nmol/L (interquartile range 36-53 nmol/L) to 131 nmol/L (interquartile range 115-147 nmol/L). This submission comprises 112 samples from 57 individuals.
Project description:We wanted to examine the effect of vitamin D3 and endogenous mutant p53 expressed in SKBR3 cells on gene expression paterns. Expression microarray analysis was performed on SKBR3 cells without or with endogenous mutp53 knockdown, with or without 1a25-vitamin D3 treatment.
Project description:Background: The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate immune responses in vivo has not been established in humans. Methods: Twenty healthy adults were randomized to receive placebo or a single high dose of vitamin D3 (cholecalciferol) one hour after localized skin irradiation with an erythemogenic dose of ultraviolet radiation. Primary outcomes included skin redness, skin thickness, and tissue expression of inflammatory mediators (TNF-α and iNOS). Secondary outcomes included microarray analyses. Results: As compared to placebo, subjects receiving vitamin D3 (200,000 IU) demonstrated reduced expression of TNF-α (p=0.04) and iNOS (p=0.02) in skin biopsies 48 hours after ultraviolet light exposure. Demonstrated trends included reduced skin redness (p=0.17), and reduced skin thickness (p=0.09) in subjects receiving vitamin D3 (200,000 IU). Unsupervised clustering of individuals based on global gene expression revealed that subjects with enhanced skin barrier repair expression profiles had higher serum vitamin D3 levels (p=0.007), increased arginase expression (p=0.005), and a sustained reduction in skin redness (p=0.02) after treatment, as compared to subjects with enhanced inflammatory gene expression profiles. Conclusions: A single high dose of oral vitamin D is capable of attenuating a local sunburn response to ultraviolet radiation, suggesting that oral vitamin D may be clinically therapeutic for its immunomodulatory properties. These results have broad implications for the role of vitamin D in skin homeostasis, and implicate arginase activation as a novel mechanism by which vitamin D exerts anti-inflammatory effects in humans.
Project description:In this study, we analyse the in-vivo modulation of the transcriptome of human PBMCs by a bolus of vitamin D3 (80,000 IU) after 24 hours.
Project description:Epidemiological data have linked vitamin D deficiency to the onset of various cancers, including prostate cancer, and although in-vitro studies have demonstrated anti-cancer activities for the vitamin, clinical trials provided conflicting results. To determine the impact of vitamin D signaling on prostatic precancerous lesions, we treated genetically-engineered mice harboring prostatic intraepithelial neoplasia (PIN) with Gemini-72, a vitamin D analogue with reported anti-cancer activities, and comprehensively analyzed its effects on various cell types in such lesions. We show that this analogue induces apoptosis in senescent PINs and normalizes extracellular matrix remodeling by stromal fibroblasts in an epithelial VDR-dependent manner. Furthermore, it reduces the prostatic infiltration of immunosuppressive myeloid-derived suppressor cells in an epithelial VDR-independent manner. Moreover, single-cell RNA-sequencing analysis demonstrates that while a subset of luminal epithelial cells, expressing Krt4 and Tacstd2 (termed luminal-C) with enhanced interferon signature, is lost by such a treatment, anti-apoptotic pathways are induced in persistent luminal-C cells. Therefore, our findings delineate the distinct responses of prostatic precancerous lesions and the microenvironment to the vitamin D analogue, and shed light on mechanisms that limit treatment’s efficacy.
Project description:Human naive T cells from peripheral blood were cultured in 24 wells coated with anti-CD3 and anti-CD28 antibodies in the presence or absence of retinoid acid, IL-12, and 1,25 (OH)2 vitamin D3. The T cells were FACS-sorted based on expression of CD3, integrin alpha4beta7, cutaneous lymphocyte antigen (CLA) and chemokine receptor 10. This serie includes microarray data from stimulated T cells under indicated conditions. Keywords: Human T cell, vitamin D and A, chemokine receptor, nuclear receptor
Project description:Pregnancy 25-hydroxyvitamin D (25(OH)D) concentrations are associated with maternal and fetal health outcomes, but the underlying mechanisms have not been elucidated. Using physiological human placental perfusion approaches and intact villous explants we demonstrate a role for the placenta in regulating the relationships between maternal 25(OH)D concentrations and fetal physiology. Here, we demonstrate active placental uptake of 25(OH)D3 by endocytosis and placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the fetal and maternal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than solely the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer, including transcriptional activation and inflammatory responses. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta; with widespread effects on the placenta itself. These data show complex and synergistic interplay between vitamin D and the placenta, and inform possible interventions to optimise placental function to better support fetal growth and the maternal adaptations to pregnancy.
Project description:Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). Both in vitro and animal studies suggest an immunomodulatory effect of vitamin D. The PrevANZ trial, a phase IIb randomized placebo-controlled trial of oral vitamin D3 supplementation in people with a first demyelinating event (FDE), was conducted to determine if supplementation can prevent recurrent disease activity in this cohort at high risk of developing definite MS. As a sub-study of this trial, we used whole blood transcriptomic analyses to investigate the effect of vitamin D3 supplementation on peripheral immune cells in people with an FDE, and to gain insight into potential mechanisms by which vitamin D3 may regulate MS risk and disease activity. The PrevANZ trial randomized participants to 1000 IU, 5000 IU or 10,000 IU daily of oral vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks in PAXgene Blood RNA tubes. Transcriptomic datasets were generated by RNA sequencing.