scholarly journals Role of glucuronidated 25-hydroxyvitamin D on colon gene expression in mice

2020 ◽  
Vol 319 (2) ◽  
pp. G253-G260
Author(s):  
Carmen J. Reynolds ◽  
Nicholas J. Koszewski ◽  
Ronald L. Horst ◽  
Donald C. Beitz ◽  
Jesse P. Goff
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

We found that 25OHD-Gluc, an endogenously produced metabolite, is delivered to the colon via bile to induce vitamin D-mediated responses in the colon.

scholarly journals THU0235 VITAMIN D AND INTERFERON SIGNATURE GENE EXPRESSION IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 344.3-345
Author(s):  
R. Magro ◽  
C. Saliba ◽  
L. Camilleri ◽  
C. Scerri ◽  
A. Borg
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Significant Negative Correlation ◽  
Systemic Lupus ◽  
Interferon Signature ◽  
Hydroxyvitamin D ◽  
Signature Genes ◽  
25 Hydroxyvitamin D

Background:Vitamin D deficiency is more prevalent in patients with systemic lupus eythematosus (SLE) as a result of sun avoidance.1The potential negative impact of vitamin D deficiency on SLE disease activity has been shown in a number of studies.2The expression of the interferon signature genes in SLE correlates positively with disease activity, and these genes are thought to mediate the clinical manifestations of the disease.3Objectives:The aim of this study was to establish whether a relationship exists between serum 25-hydroxyvitamin D level and the interferon signature gene expression in whole blood of SLE patients.Methods:Informed consent was obtained from 92 SLE patients who were over the age of 18 and who fulfilled the SLICC classification criteria for SLE. The patients were interviewed and blood samples were taken. SLE disease activity was measured by SLE disease activity index-2K (SLEDAI-2K). RNA extraction was performed from whole blood. QuantiGene Plex technology was used to measure the expression of 12 interferon signature genes in the extracted RNA. The study was approved by the University Research Ethics Committee.Results:92.4% of the cohort studied were female. 58.7% were receiving vitamin D3 supplementation at a mean dose of 1031IU daily. 27.2% had vitamin D insufficiency (25-hydroxyvitamin D 21-29ng/ml) and 15.2% were vitamin D deficient (25-hydroxyvitamin D <20ng/ml). Mean serum 25-hydroxyvitamin D was 30.75ng/ml (standard deviation 9.53 ng/ml). Median SLEDAI-2K was 4 (range 0-12). Serum 25-hydroxyvitamin D had a significant negative correlation with body mass index (BMI) (R=-0.258, p=0.006) but there was no significant negative correlation with SLEDAI-2K or with the expression of the interferon signature genes. The expression of most interferon signatures genes measured (IFI35, OAS1, MX1, IFITM1, STAT2, IFIT3, IFIT1, STAT1, SOCS1) had a significant positive correlation with SLEDAI-2K.Conclusion:This study did not show a significant relationship between serum vitamin D level and disease activity. In keeping with this, there was no significant negative correlation between serum 25-hydroxyvitamin D and interferon signature gene expression. Further prospective studies and randomised controlled trials are required to study this relationship in greater depth.References:[1]Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev. 2006; 5: 114-7.[2]Sahebari M, Nabavi N, Salehi M. Correlation between serum 25(OH)D values and lupus disease activity: an original article and a systematic review with meta-analysis focusing on serum VitD confounders.Lupus2014; 23: 1164-77.[3]Arasappan D, Tong W, Mummaneni P, Fang H, Amur S. Meta-analysis of microarray data using a pathway-based approach identifies a 37-gene expression signature for systemic lupus erythematosus in human peripheral blood mononuclear cells. BMC Med. 2011; 9: 65.Disclosure of Interests: :None declared

scholarly journals Response of the 5′-flanking region of the human 25-hydroxyvitamin D 1α-hydroxylase gene to physiological stimuli using a transgenic mouse model

2005 ◽  
Vol 34 (1) ◽  
pp. 237-245 ◽  
Author(s):  
I Hendrix ◽  
P H Anderson ◽  
J L Omdahl ◽  
B K May ◽  
H A Morris
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Transgenic Mouse ◽  
Reporter Gene ◽  
Dietary Calcium ◽  
Mrna Levels ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Flanking Region

The enzyme 25-hydroxyvitamin D 1α-hydroxylase, or CYP27B1, is the key enzyme in the two-step activation process of vitamin D to 1,25-dihydroxyvitamin D (1,25D). While a number of regulators of the renal CYP27B1 enzyme activity have been recognized for some years, their underlying molecular mechanisms remain largely unknown, and the DNA regions involved in the in vivo regulation of gene expression by these factors have not been delineated. We have generated a transgenic mouse line that expresses 1501 bp of 5′ flanking region together with 44 bp of 5′ untranslated region of the human CYP27B1 gene fused to the firefly luciferase reporter gene. Animals expressing the luciferase gene demonstrated that both luciferase protein and mRNA for CYP27B1 were localized to proximal convoluted tubule cells of the kidney. In 2-week-old animals, the expression of the transgene and the endogenous CYP27B1 mRNA levels in the kidney were highest and fell with increasing age. Both reporter gene expression and CYP27B1 mRNA levels were downregulated in response to increasing amounts of dietary calcium in a dose-dependent manner. Vitamin D deficiency resulted in an increase in both the reporter gene and CYP27B1 expression. Interestingly, the increase in CYP27B1 mRNA levels was substantially higher than the increase in reporter gene expression, suggesting either that there is a post-transcriptional mechanism that increases the amount of CYP27B1 mRNA or that other regulatory elements are required to maximize the effect of vitamin D deficiency. These findings demonstrate that the 1501 bp 5′ flanking region of the CYP27B1 gene directs expression to the proximal convoluted tubules of the kidney and is responsible for increasing transcriptional activity when dietary calcium and vitamin D levels are depleted. It also responds in the kidney to the physiological regulators of development and ageing.

Role of vitamin D and sFlt-1/PlGF ratio in the development of early- and late-onset preeclampsia

2015 ◽  
Vol 53 (7) ◽  
Author(s):  
Indira Álvarez-Fernández ◽  
Belén Prieto ◽  
Verónica Rodríguez ◽  
Yolanda Ruano ◽  
Ana I. Escudero ◽  
...  
Keyword(s):  
Vitamin D ◽  
Late Onset ◽  
Tertiary Care ◽  
Care Hospital ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D ◽  
The Relationship ◽  
Plgf Ratio

AbstractThe imbalanced production of placental biomarkers and vitamin D deficiency have been proposed as risk factors for the development of preeclampsia (PE). However, little is known about the relationship between them and their role in early- versus late-onset PE. The objectives were to assess the role of 25-hydroxyvitamin D [25(OH)D] concentrations and the soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio in the development of early- and late-onset PE; and to evaluate the relationship between 25(OH)D and the biomarkers.A retrospective, full-blinded cohort study was conducted at the Obstetric Emergency Service of a tertiary care hospital. Pregnant women (n=257) attending obstetric triage with suspicion of PE were included. sFlt-1, PlGF and 25(OH)D concentrations were measured by electrochemoluminescence (ECLIA) immunoassay and pregnancy outcome (development of PE) was registered from patients records.PE women showed lower 25(OH)D concentrations at clinical presentation than non-PE women (median: 35.0 nmol/L and 39.6 nmol/L, respectively; p=0.027). Women with 25(OH)D levels <50 nmol/L experienced an increased risk of developing late-onset PE [odds ratio (OR) 4.6, 95% confidence interval (CI) 1.4–15], but no association was found for early-onset PE. However, a sFlt-1/PlGF ratio above the corresponding cutpoints increased the risk of developing both early- and late-onset PE [ORs 58 (95% CI 11–312) and 12 (95% CI 5.0–27), respectively]. No association was found between 25(OH)D levels and sFlt-1/PlGF ratio.Low vitamin D status in women with suspected late-onset PE increases the risk of imminent development of the disease.

scholarly journals Role of the vitamin D receptor in FGF23 action on phosphate metabolism

2005 ◽  
Vol 390 (1) ◽  
pp. 325-331 ◽  
Author(s):  
Yoshio Inoue ◽  
Hiroko Segawa ◽  
Ichiro Kaneko ◽  
Setsuko Yamanaka ◽  
Kenichiro Kusano ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Fibroblast Growth Factor 23 ◽  
Mrna Levels ◽  
Dna Encoding ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Naked Dna ◽  
25 Hydroxyvitamin D

FGF23 (fibroblast growth factor 23) is a novel phosphaturic factor that influences vitamin D metabolism and renal re-absorption of Pi. The goal of the present study was to characterize the role of the VDR (vitamin D receptor) in FGF23 action using VDR(−/−) (VDR null) mice. Injection of FGF23M (naked DNA encoding the R179Q mutant of human FGF23) into VDR(−/−) and wildtype VDR(+/+) mice resulted in an elevation in serum FGF23 levels, but had no effect on serum calcium or parathyroid hormone levels. In contrast, injection of FGF23M resulted in significant decreases in serum Pi levels, renal Na/Pi co-transport activity and type II transporter protein levels in both groups when compared with controls injected with mock vector or with FGFWT (naked DNA encoding wild-type human FGF23). Injection of FGF23M resulted in a decrease in 25-hydroxyvitamin D 1α-hydroxylase mRNA levels in VDR(−/−) and VDR(+/+) mice, while 25-hydroxyvitamin D 24-hydroxylase mRNA levels were significantly increased in FGF23M-treated animals compared with mock vector control- or FGF23WT-treated animals. The degree of 24-hydroxylase induction by FGF23M was dependent on the VDR, since FGF23M significantly reduced the levels of serum 1,25(OH)2D3 [1,25-hydroxyvitamin D3] in VDR(+/+) mice, but not in VDR(−/−) mice. We conclude that FGF23 reduces renal Pi transport and 25-hydroxyvitamin D 1α-hydroxylase levels by a mechanism that is independent of the VDR. In contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction of serum 1,25(OH)2D3 levels induced by FGF23 are dependent on the VDR.

scholarly journals The Role of the Intraplaque Vitamin D System in Atherogenesis

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Federico Carbone ◽  
Fabrizio Montecucco
Keyword(s):  
Vitamin D ◽  
Clinical Findings ◽  
Peripheral Tissues ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Mouse Tissues ◽  
Calcium Phosphorus ◽  
25 Hydroxyvitamin D ◽  
Physiological Pathways

Vitamin D has been shown to play critical activities in several physiological pathways not involving the calcium/phosphorus homeostasis. The ubiquitous distribution of the vitamin D receptor that is expressed in a variety of human and mouse tissues has strongly supported research on these “nonclassical” activities of vitamin D. On the other hand, the recent discovery of the expression also for vitamin D-related enzymes (such as 25-hydroxyvitamin D-1α-hydroxylase and the catabolic enzyme 1,25-dihydroxyvitamin D-24-hydroxylase) in several tissues suggested that the vitamin D system is more complex than previously shown and it may act within tissues through autocrine and paracrine pathways. This updated model of vitamin D axis within peripheral tissues has been particularly investigated in atherosclerotic pathophysiology. This review aims at updating the role of the local vitamin D within atherosclerotic plaques, providing an overview of both intracellular mechanisms and cell-to-cell interactions. In addition, clinical findings about the potential causal relationship between vitamin D deficiency and atherogenesis will be analysed and discussed.

scholarly journals Prevalence of vitamin D deficiency and insufficiency among schoolchildren in Greece: the role of sex, degree of urbanisation and seasonality

2017 ◽  
Vol 118 (7) ◽  
pp. 550-558 ◽  
Author(s):  
Yannis Manios ◽  
George Moschonis ◽  
Toine Hulshof ◽  
Anne-Sophie Bourhis ◽  
George L. J. Hull ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Urban Areas ◽  
Urban Region ◽  
Vitamin D Status ◽  
Hydroxyvitamin D ◽  
Primary Schoolchildren ◽  
Region Of Residence ◽  
25 Hydroxyvitamin D

AbstractThe current study was aiming to report the prevalence of suboptimal vitamin D status among schoolchildren in Greece and investigate the role of sex, urbanisation and seasonality on vitamin D status. A sample of 2386 schoolchildren (9–13 years old) from four distinct prefectures was examined. The prevalence of 25-hydroxyvitamin D (25(OH)D) concentration <30 and <50 nmol/l (vitamin D deficiency and insufficiency respectively) was 5·2 and 52·5 %, respectively. Girls had a higher prevalence of 25(OH)D<30 (7·2 v. 3·2 %) and 50 nmol/l (57·0 v. 48·0 %) than boys (P<0·001). The highest prevalence rates of 25(OH)D<30 and 50 nmol/l (9·1 and 73·1 %, respectively) were observed during spring (April to June), whereas the lowest (1·5 and 31·9 %, respectively) during autumn (October to December). The prevalence of 25(OH)D<50 nmol/l was higher in urban/semi-urban than rural regions, particularly during spring months (74·6 v. 47·2 %; P<0·001). Female sex, urban/semi-urban region of residence and spring months were found to increase the likelihood of vitamin D deficiency and insufficiency, with the highest OR observed for spring months (7·47; 95 % CI 3·23, 17·3 and 5·14; 95 % CI 3·84, 6·89 for 25(OH)D<30 and 50 nmol/l respectively). In conclusion, despite the southerly latitude, the prevalence of low vitamin D status among primary schoolchildren in Greece is comparable to or exceeds the prevalence reported among children and adolescents on a European level. Sub-populations at highest risk are girls in urban/semi-urban areas during spring months, thus indicating the need for effective initiatives to support adequate vitamin D status in these population groups.

scholarly journals Serum 25-Hydroxyvitamin D and Adipose Tissue Vitamin D Receptor Gene Expression: Relationship With Obesity and Type 2 Diabetes

2015 ◽  
Vol 100 (4) ◽  
pp. E591-E595 ◽  
Author(s):  
Mercedes Clemente-Postigo ◽  
Araceli Muñoz-Garach ◽  
Marta Serrano ◽  
Lourdes Garrido-Sánchez ◽  
M. Rosa Bernal-López ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Receptor Gene ◽  
Vitamin D Receptor Gene ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Receptor Gene Expression ◽  
Tissue Vitamin

scholarly journals Role of Vitamin D in Preeclampsia

2021 ◽  
Author(s):  
Simmi Kharb
Keyword(s):  
Vitamin D ◽  
Immune Dysfunction ◽  
Vitamin D Supplementation ◽  
Vitamin D Status ◽  
Infant Outcomes ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Vitamin D Signaling ◽  
Maternal And Infant Outcomes

Pathogenesis of preeclampsia involves immune dysfunction, placental implantation, abnormal angiogenesis, excessive inflammation, hypertension that may be affected by vitamin D. Human placenta expresses all the components for vitamin D signaling: Vitamin D receptor (VDR), retinoid X receptor (RXR), 1-alpha- hydroxylase (CYP27B1) and 24- hydroxylase (CYP24A1). Vitamin D binding protein plays a role in binding and transportation of 25 hydroxyvitamin D [25(OH)D] and 1,25(OH)2D3. Vitamin D is activated by 25-hydroxylase (CYP2R1) and 1-alpha -hydroxylase (CYP27B1) and is degraded by 24-hydroxylase (CYP24A1). Vitamin D supplementation is not recommended by WHO for pregnant women and allows recommended nutrient intake (RNI) of 200 IU (5 μg) per day. Further research requires serum 25(OH)D analysis and assessment of maternal and infant outcomes; pre-conceptional vitamin D status.

scholarly journals Effects of Cholecalciferol on Key Components of Vitamin D-Endo/Para/Autocrine System in Experimental Type 1 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Anna Mazanova ◽  
Ihor Shymanskyi ◽  
Olha Lisakovska ◽  
Lala Hajiyeva ◽  
Yulia Komisarenko ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Vitamin D Deficiency ◽  
Diabetic Rats ◽  
Hydroxyvitamin D ◽  
Male Wistar Rats ◽  
Experimental Type ◽  
25 Hydroxyvitamin D

Objectives.Recent prospective studies have found the associations between type 1 diabetes (T1D) and vitamin D deficiency. We investigated the role of vitamin D in the regulation of 25OHD-1α-hydroxylase (CYP27B1) and VDR expression in different tissues of T1D rats.Design.T1D was induced in male Wistar rats by streptozotocin (55 mg/k b.w.). After 2 weeks of T1D, the animals were treated orally with or without vitamin D3(cholecalciferol; 100 IU/rat, 30 days).Methods.Serum 25-hydroxyvitamin D (25OHD) was detected by ELISA. CYP27A1, CYP2R1, CYP27B1, and VDR were assayed by RT-qPCR and Western blotting or visualized by immunofluorescence staining.Results.We demonstrated that T1D led to a decrease in blood 25OHD, which is probably due to the established downregulation of CYP27A1 and CYP2R1 expression. Vitamin D deficiency was accompanied by elevated synthesis of renal CYP27B1 and VDR. Conversely, CYP27B1 and VDR expression decreased in the liver, bone tissue, and bone marrow. Cholecalciferol administration countered the impairments of the vitamin D-endo/para/autocrine system in the kidneys and extrarenal tissues of diabetic rats.Conclusions.T1D-induced vitamin D deficiency is associated with impairments of renal and extrarenal CYP27B1 and VDR expression. Cholecalciferol can be effective in the amelioration of diabetes-associated abnormalities in the vitamin D-endo/para/autocrine system.

scholarly journals Vitamin D Supplementation in Sarcoidosis: A Double-Edged Sword

2021 ◽  
Author(s):  
Rishikesh Chandran ◽  
Lakshmi Nagendra ◽  
Shrikrishna Acharya ◽  
Giridhar Belur Hosmane ◽  
Vijith Shetty ◽  
...  
Keyword(s):  
Vitamin D ◽  
Disease Activity ◽  
Bone Health ◽  
Calcium Metabolism ◽  
Vitamin D Supplementation ◽  
Osteoporosis Prevention ◽  
Hydroxyvitamin D ◽  
Severe Hypercalcemia ◽  
25 Hydroxyvitamin D

AbstractSarcoidosis is complicated by disordered vitamin D and calcium metabolism, which has important implications on disease activity and bone health. Although the majority of the patients with sarcoidosis are typically deficient in 25-hydroxyvitamin D, repletion of vitamin D is controversial in light of the hypercalcemia risk. Presently, there are no clear guidelines regarding vitamin D supplementation as a part of osteoporosis prevention in patients with vitamin D deficiency and sarcoidosis. We report a patient with sarcoidosis who presented with severe hypercalcemia following vitamin D supplementation and review the debated role of vitamin D supplementation in vitamin D-deficient sarcoid patients.

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