Vitamin D Receptor Expression in Dogs

Cartwright, Jennifer A; Gow, Adam; Milne, Elspeth; Drummond, D.; Smith, Sionagh; Handel, Ian; Mellanby, Richard J.

doi:10.1111/jvim.15052

Cited by 23 publications

(19 citation statements)

References 72 publications

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“…One study measured lower vitamin D levels in cats with IBD and intestinal lymphoma (36). Chronic kidney disease can eventually result in lower plasma 1,25(OH)2D3 due to reductions in synthesis (34, 37). Thus, vitamin D status can be altered in cats and dogs secondary to inflammation, decreased absorption or synthesis and increased loss.…”

Section: Discussionmentioning

confidence: 99%

Serum Vitamin D Metabolites and CXCL10 Concentrations Associate With Survival in Dogs With Immune Mediated Disease

2019

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Background: Low vitamin D increases the risk of immune-mediated disease (IMD) in human beings and rodent models. Vitamin D metabolites, particularly 1,25(OH)2D3, modulate gene expression of immune cells and may attenuate immune pathways that drive IMD. Hypothesis/objectives: Our primary hypothesis was that serum 25(OH)D3 and 1,25(OH)2D3, are reduced in patients with IMD and associate with poorer outcomes. We secondarily hypothesized serum 24,25(OH)2D3 would not be associated with disease or outcome. We also measured serum CXCL10 concentrations to determine if an increase occurs in dogs with IMD and in association with poorer survival. Animals: We enrolled dogs diagnosed with IMD ( n = 29) and healthy control dogs ( n = 9) in the study with informed client consent. Methods: Serum was collected and stored at −80°C until analyses. Serum vitamin D metabolites were measured by LC-MS/MS by an accredited laboratory. A commercially available canine-specific ELISA kit measured serum CXCL10. Results: Serum 25(OH)D3 and 1,25(OH)2D3 were significantly reduced in dogs ( n = 25) with IMD. Serum CXCL10 concentrations undetectable in all controls, and were 30 times higher overall in IMD dogs ( n = 25; P = 0.004). CXL10 was, however, undetectable in 40% of dogs with IMD. Of the 60% of IMD dogs with increased CXCL10 concentrations, 5/25 had concentrations at the upper limit of quantification. The survival of those five dogs was significantly ( P = 0.049) shorter (72 days) than all other dogs with IMD with measured CXCL10 concentrations. The median survival time (MST) for dogs with 25(OH)D3 concentrations ≤ the median was 106 days, while dogs with concentrations of 25(OH)D3 > the median did not achieve an MST. Conclusions and clinical importance: Serum 25(OH)D3 and 1,25(OH)2D3, but not 24,25(OH)2D3 levels are reduced dogs with IMD. Vitamin D metabolites and CXCL10 may be useful prognostic markers and may be targets for adjunct therapy in canine IMD. These data support the future investigation of vitamin D analogs in the treatment of canine IMD.

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Section: Discussionmentioning

confidence: 99%

Serum Vitamin D Metabolites and CXCL10 Concentrations Associate With Survival in Dogs With Immune Mediated Disease

2019

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“…Quantitative PCR analysis of target gene was executed using Biorad CFX96 Real time-PCR taking human housekeeping gene, GAPDH as a reference. Previously reported primers for qPCR analysis of target and reference gene were selected for this study 78 , 79 following the standard protocol 80 . Relative gene expression analysis from qPCR data was performed using the Relative Expression Software Tool (REST® 2009) 81 that utilises the expression of reference genes to normalize expression of target genes in different samples.…”

Section: Methodsmentioning

confidence: 99%

Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach

Verma

Sharda

Rathi

et al. 2020

Sci Rep

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Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g. Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia have been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe ‘interspecies communication’, using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA. Our study identified Na(+)/H(+) anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies.

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“…Although VDR is widely expressed in all tissues in dogs, the colon of healthy dogs is the only place where its expression is weak, unlike humans and other species (Cartwright et al, 2018). In humans and mice used as an experimental model for ulcerative colitis, the VDR expression was negatively related to colonic inflammation; however, in studies carried out by Cartwright et al (2018) no changes in VDR expression were observed in dogs with inflammatory bowel disease. The authors also observed that the expression of VDR was not correlated with the presence of inflammation, which, may confer an advantage for the treatment of these animals with vitamin D replacement.…”

Section: Vitamin D and Gastrointestinal Diseasesmentioning

confidence: 99%

“…Finally, this may still have a positive effect on the expression of FOXP3 and the formation of induced regulatory T cells (Mora et al, 2008). Although VDR is widely expressed in all tissues in dogs, the colon of healthy dogs is the only place where its expression is weak, unlike humans and other species (Cartwright et al, 2018). In humans and mice used as an experimental model for ulcerative colitis, the VDR expression was negatively related to colonic inflammation; however, in studies carried out by Cartwright et al (2018) no changes in VDR expression were observed in dogs with inflammatory bowel disease.…”

Section: Vitamin D and Gastrointestinal Diseasesmentioning

confidence: 99%

Vitamin D metabolism in dogs and cats and its relation to diseases not associated with bone metabolism

Zafalon

Risolia

Pedrinelli

et al. 2019

Animal Physiology Nutrition

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Due to the presence of receptors in the cells of numerous body tissues, vitamin D is associated with several physiological functions that go beyond calcium and phosphorus homoeostasis and control of bone metabolism in the body. In humans, several studies have associated lower vitamin D concentrations with numerous diseases, such as cancer, heart disease, autoimmune diseases and infectious diseases, and also with an increase in the total mortality rate of the population. Recently, this nutrient started to gain importance in veterinary medicine, and several articles have shown a correlation between low vitamin D status and diseases unrelated to bone metabolism. The present review aims to highlight the recent publications that investigated this relationship, bringing the evidence that exists so far in dogs and cats. K E Y W O R D S1,25(OH)2D, 25(OH)D, calcidiol, calcitriol, cholecalciferol, hypovitaminosis D

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Vitamin D Receptor Expression in Dogs

Cited by 23 publications

References 72 publications

Serum Vitamin D Metabolites and CXCL10 Concentrations Associate With Survival in Dogs With Immune Mediated Disease

Serum Vitamin D Metabolites and CXCL10 Concentrations Associate With Survival in Dogs With Immune Mediated Disease

Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach

Vitamin D metabolism in dogs and cats and its relation to diseases not associated with bone metabolism

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