Long-term vitamin D deficiency promotes renal fibrosis and functional impairment in middle-aged male mice

2020 ◽  
pp. 1-10
Author(s):  
Zhi-Hui Zhang ◽  
Biao Luo ◽  
Shen Xu ◽  
Zhi-Cheng Zhang ◽  
Wei-Yang Xing ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Functional Impairment ◽  
Renal Fibrosis ◽  
Male Mice ◽  
Middle Aged ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Middle Aged Male

Abstract Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial–mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.

The role of 1,25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency

1992 ◽  
Vol 37 (1) ◽  
pp. 17-27 ◽  
Author(s):  
M. R. Clements ◽  
M. Davies ◽  
M. E. Hayes ◽  
Claire D. Hlckey ◽  
G. A. Lumb ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

scholarly journals Active Vitamin D (1,25-Dihydroxyvitamin D) and Bone Health in Middle-Aged and Elderly Men: The European Male Aging Study (EMAS)

2013 ◽  
Vol 98 (3) ◽  
pp. 995-1005 ◽  
Author(s):  
Dirk Vanderschueren ◽  
Stephen R. Pye ◽  
Terence W. O'Neill ◽  
David M. Lee ◽  
Ivo Jans ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Health ◽  
Active Vitamin ◽  
Middle Aged ◽  
Elderly Men ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Active Vitamin D ◽  
Aging Study

scholarly journals Vitamin D deficiency osteomalacia triggered by long-term social withdrawal and unbalanced diet in a Japanese middle-aged subject

Medicine ◽  
2022 ◽  
Vol 101 (2) ◽  
pp. e28589
Author(s):  
Yuichiro Iwamoto ◽  
Fuminori Tatsumi ◽  
Kazunori Dan ◽  
Yukino Katakura ◽  
Masashi Shimoda ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Social Withdrawal ◽  
Middle Aged ◽  
Aged Subject ◽  
Unbalanced Diet

scholarly journals Effect of a Single Oral Dose of 600,000 IU of Cholecalciferol on Serum Calciotropic Hormones in Young Subjects with Vitamin D Deficiency: A Prospective Intervention Study

2010 ◽  
Vol 95 (10) ◽  
pp. 4771-4777 ◽  
Author(s):  
Cristiana Cipriani ◽  
Elisabetta Romagnoli ◽  
Alfredo Scillitani ◽  
Iacopo Chiodini ◽  
Rita Clerico ◽  
...  
Keyword(s):  
Vitamin D ◽  
Young People ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Vitamin D Deficiency ◽  
Intervention Study ◽  
Ambulatory Care Setting ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Young Subjects

Context: Effects of vitamin D repletion in young people with low vitamin D status have not been investigated so far. Objective: We evaluated the effect of a single massive dose of cholecalciferol on calcium metabolism at 3, 15, and 30 d, compared to baseline. Design and Setting: We conducted a prospective intervention study in an ambulatory care setting. Participants: Forty-eight young subjects with vitamin D deficiency participated in the study. Intervention: A single oral dose of 600,000 IU of cholecalciferol was administered to each subject. Main Outcome Measures: We evaluated serum changes of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, calcium, and PTH induced by a single load of cholecalciferol. Results: The 25(OH)D level was 15.8 ± 6.5 ng/ml at baseline and became 77.2 ± 30.5 ng/ml at 3 d (P < 0.001) and 62.4 ± 26.1 ng/ml at 30 d (P < 0.001). PTH levels concomitantly decreased from 53.0 ± 20.1 to 38.6 ± 17.2 pg/ml at 3 d and to 43.4 ± 14.0 pg/ml at 30 d (P < 0.001 for both). The trends were maintained in a subgroup followed up to 90 d (P < 0.001). Mean serum Ca and P significantly increased compared to baseline, whereas serum Mg decreased at 3 d. 1,25-Dihydroxyvitamin D significantly increased from 46.8 ± 18.9 to 97.8 ± 38.3 pg/ml at 3 d (P < 0.001) and to 59.5 ± 27.3 pg/ml at 60 d (P < 0.05). Conclusions: A single oral dose of 600,000 IU of cholecalciferol rapidly enhances 25(OH)D and reduces PTH in young people with vitamin D deficiency.

scholarly journals Relationship between 1,25-Dihydroxyvitamin D and Body Composition in Middle-Aged Sedentary Adults: The FIT-AGEING Study

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2567 ◽  
Author(s):  
Alejandro De-la-O ◽  
Lucas Jurado-Fasoli ◽  
Manuel J. Castillo ◽  
Luis Gracia-Marco ◽  
Ángel Gutierrez ◽  
...  
Keyword(s):  
Vitamin D ◽  
Body Composition ◽  
Body Mass ◽  
Fat Body ◽  
Middle Aged ◽  
Mineral Density ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Wide Range ◽  
Fat Body Mass

Vitamin D deficiency is a worldwide health problem that, in addition to its well-known negative effects on musculoskeletal health, has been related to a wide range of acute and chronic age-related diseases. However, little is known about the association of body composition with the active, hormonal form of vitamin D, 1,25-dihydroxyvitamin D plasma levels (1,25(OH)2D). Therefore, the aim of this study was to investigate the association of 1,25(OH)2D with body composition including lean and fat body mass as well as bone mineral density (BMD) in middle-aged sedentary adults. A total of 73 (39 women) middle-aged sedentary adults (53.7 ± 5.1 years old) participated in the current study. We measured weight and height, and we used dual energy X-ray absorptiometry to measure lean body mass, fat body mass and BMD. Body mass index (BMI), lean mass index (LMI), and fat mass index (FMI) were calculated. 1,25(OH)2D was measured using a DiaSorin Liaison® immunochemiluminometric analyzer. The results showed a negative association of 1,25(OH)2D with BMI, LMI and BMD (β = −0.274, R2 = 0.075, p = 0.019; β = −0.268, R2 = 0.072, p = 0.022; and β = −0.325, R2 = 0.105, p = 0.005, respectively), which persisted after controlling for age and sex. No significant differences in 1,25(OH)2D across body weight status were observed after controlling for the same covariates. In summary, our results suggest that 1,25(OH)2D could be negatively associated with BMI, LMI and BMD whereas no association was found with FMI in middle-aged sedentary adults.

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation

2018 ◽  
Vol 31 (8) ◽  
pp. 861-868 ◽  
Author(s):  
Muhammad Faiyaz-Ul-Haque ◽  
Waheeb AlDhalaan ◽  
Abdullah AlAshwal ◽  
Bassam S. Bin-Abbas ◽  
Afaf AlSagheir ◽  
...  
Keyword(s):  
Vitamin D ◽  
Target Genes ◽  
Clinical Symptoms ◽  
Active Form ◽  
Loss Of Function ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Vitamin D Resistant Rickets ◽  
Resistant Rickets

Abstract Background: Vitamin D regulates the concentrations of calcium and phosphate in blood and promotes the growth and remodeling of bones. The circulating active form of vitamin D, 1,25-dihydroxyvitamin D, binds to the vitamin D receptor (VDR), which heterodimerizes with the retinoid X receptor to regulate the expression of target genes. Inactivating mutations in the VDR gene cause hereditary vitamin D-resistant rickets (HVDRR), a rare disorder characterized by an early onset of rickets, growth retardation, skeletal deformities, hypocalcemia, hypophosphatemia and secondary hyperparathyroidism, and in some cases alopecia. Methods: We describe eight new HVDRR patients from four unrelated consanguineous families. The VDR gene was sequenced to identify mutations. The management of patients over a period of up to 11 years following the initial diagnosis is assessed. Results: Although all patients exhibit main features of HVDRR and carry the same c.885C>A (p.Y295*) loss of function mutation in the VDR gene, there was heterogeneity of the manifestations of HVDRR-associated phenotypes and developmental milestones. These eight patients were successfully treated over a period of 11 years. All clinical symptoms were improved except alopecia. Conclusions: The study concludes that VDR sequencing and laboratory tests are essential to confirm HVDRR and to assess the effectiveness of the treatment.

scholarly journals Association of serum 25-hydroxyvitamin D with metabolic syndrome and type 2 diabetes: a one sample Mendelian randomization study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Xiao ◽  
Jingyi Lv ◽  
Shiyu Wang ◽  
Yang Zhou ◽  
Lunwen Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Mendelian Randomization ◽  
Middle Aged ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Randomization Analysis

Abstract Background Vitamin D deficiency has been associated with type 2 diabetes (T2D) and metabolic syndrome (MS) and its components. However, it is unclear whether a low concentration of vitamin D is the cause or consequence of these health conditions. Thus, this study aimed to evaluate the association of vitamin D concentrations and its genetic risk scores (GRSs) with MS and its component diseases, such as T2D, in middle-aged and elderly participants from rural eastern China. Methods A subset of 2393 middle-aged and elderly individuals were selected from 70,458 participants of the Nantong Chronic Diseases Study of 2017–2018 in China. We used two 25-hydroxyvitamin D (25[OH]D) synthesis single-nucleotide polymorphisms (SNPs) (DHCR7-rs12785878 and CYP2R1-rs10741657) and two 25(OH) D metabolism SNPs (GC-rs2282679 and CYP24A1-rs6013897) for creating GRSs, which were used as instrumental variables to assess the effect of genetically lowered 25(OH) D concentrations on MS and T2D based on the Wald ratio. F statistics were used to validate that the four SNPs genetically determined 25(OH) D concentrations. Results Compared to vitamin D sufficient individuals, individuals with vitamin D insufficiency had an odds ratio (OR [95% confidence interval {CI}]) of MS of 1.30 (1.06–1.61) and of T2D of 1.32 (1.08–1.64), individuals with vitamin D deficiency had an ORs (95% CI) of MS of 1.50 (1.24–1.79) and of T2D of 1.47 (1.12–1.80), and those with vitamin D severe deficiency had an ORs (95% CI) of MS of 1.52 (1.29–1.85) and of T2D of 1.54 (1.27–1.85). Mendelian randomization analysis showed a 25-nmol/L decrease in genetically instrumented serum 25(OH) D concentrations using the two synthesis SNPs (DHCR7 and CYP2R1 genes) associated with the risk of T2D and abnormal diastolic blood pressure (DBP) with ORs of 1.10 (95%CI: 1.02–1.45) for T2D and 1.14 (95%CI: 1.03–1.43) for DBP. Conclusions This one sample Mendelian randomization analysis shows genetic evidence for a causal role of lower 25(OH) D concentrations in promoting of T2D and abnormal DBP in middle-aged and elderly participants from rural China.

scholarly journals Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review

2021 ◽  
Vol 22 (10) ◽  
pp. 5145
Author(s):  
Giuseppe Schepisi ◽  
Caterina Gianni ◽  
Sara Bleve ◽  
Silvia De Padova ◽  
Cecilia Menna ◽  
...  
Keyword(s):  
Vitamin D ◽  
Testicular Cancer ◽  
Vitamin D Deficiency ◽  
Molecular Mechanisms ◽  
Hypovitaminosis D ◽  
Young Males ◽  
Report Data ◽  
Testicular Cancer Survivors ◽  
Patients Experience

Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications.

scholarly journals Two Vitamin D Response Elements Function in the Rat 1,25-Dihydroxyvitamin D 24-Hydroxylase Promoter

1995 ◽  
Vol 270 (4) ◽  
pp. 1675-1678 ◽  
Author(s):  
Claudia Zierold ◽  
Hisham M. Darwish ◽  
Hector F. DeLuca
Keyword(s):  
Vitamin D ◽  
Response Elements ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Measurement of Plasma 1,25 Dihydroxyvitamin D Using a Novel Immunoextraction Technique and Immunoassay with Iodine Labelled Vitamin D Tracer

1997 ◽  
Vol 34 (6) ◽  
pp. 632-637 ◽  
Author(s):  
W D Fraser ◽  
B H Durham ◽  
J L Berry ◽  
E B Mawer
Keyword(s):  
Vitamin D ◽  
Solid Phase ◽  
Plasma Concentrations ◽  
Sample Volume ◽  
Cross Reactivity ◽  
Regression Equations ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
High Concentrations

We evaluated a novel assay for the measurement of 1,25 dihydroxyvitamin D (1,25 (OH)2D). Immunoextraction of 1,25 (OH)2D is performed using a mini column containing a solid-phase monoclonal antibody followed by radioimmunoassay (RIA) using an 125I-labelled 1,25 (OH)2D derivative tracer and Sac-cell separation. The mean recovery of 1,25(OH)2D3 was 101%, linearity was excellent, inter- and intra-assay coefficients of variation were 9, 8 and 13% and 11, 10 and 14% at low, medium and high concentrations of 1,25(OH)2D3, respectively. The cross-reactivity of vitamin D metabolites was <0·0015% for 25-hydroxyvitamin D3, 24, 25 dihydroxyvitamin D3 and dihydrotachysterol and 0·54% for lα calcidol. 1,25 dihydroxyvitamin D2 cross-reactivity was 79%. The detection limit of the assay was 5pmol/L. Comparison with a commercial radio receptor assay (RRA) and an in-house RIA gave regression equations of y = 0·94x+11·8 ( r = 0·98) and y = 0·91x-1·7 ( r = 0.95), respectively, with no major discrepancies between the methods in all patient groups studied. Plasma concentrations of 1,25 (OH)2D obtained with the assay were as follows: normal, unsupplemented subjects: mean 88, range 48–155 pmol/L, n = 68, patients with chronic renal failure: mean 11, range 3–36 pmol/L, n = 27, primary hyperparathyroidism: mean 198, range 130–299 pmol/L, n = 23, Paget's disease: mean 92, range 42–149 pmol/L, n = 24, osteomalacia: mean 43, range 27–61 pmol/L, n = 9. A minimum sample volume of 300 μL is required, the hands-on time is significantly less than other commercial assays and the measuring procedure is gamma counting rather than scintillation counting. The assay offers several advantages over previous methods and should allow more laboratories to offer measurement of 1,25 (OH)2D as part of their repertoire.

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