Localisation of vitamin D receptor in normal human duodenum and in patients with coeliac disease.

Colston, Kay W.; Mackay, A. G.; Finlayson, C.; Wu, Julie C.Y.; Maxwell, J. D.

doi:10.1136/gut.35.9.1219

Cited by 58 publications

(36 citation statements)

References 26 publications

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“…The molecular action of the 1,25(OH) 2 D 3 ligand is predominantly in the nucleus Stumpf, 1995], and because VDR has been found to occur as a nuclear protein via immunocytochemistry [Berger et al, 1988;Bidwell et al, 1994;Clemens et al, 1988;Colston et al, 1994;Milde et al, 1989;Tuohimaa et al, 1992], it is apparent that VDR contains one or more nuclear localization signals. NLSs often are comprised of basic amino acids and, in addition to a series of small segments of basic amino acids distributed between residues 70 and 111 of hVDR [Luo et al, 1994], there exists an array of five basic amino acids between residues 49 and 55 (Fig.…”

Section: Conserved Basic Amino Acid Sequences Among the Nuclear Proteinsmentioning

confidence: 99%

Novel nuclear localization signal between the two DNA-binding zinc fingers in the human vitamin D receptor

et al. 1998

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The human vitamin D receptor (hVDR) possesses a unique array of five basic amino acids positioned between the two DNA-binding zinc fingers that is similar to well-characterized nuclear localization sequences in other proteins. When residues within this region are mutated to nonbasic amino acids, or when this domain is deleted, the receptor is still well expressed, but it no longer associates with the vitamin D-responsive element in DNA, in vitro, and hVDR-mediated transcriptional activation is abolished in transfected cells. Concomitantly, the mutated hVDRs exhibit a significant shift in hVDR cellular distribution favoring cytoplasmic over nuclear retention as assessed by subcellular fractionation and immunoblotting. Independent immunocytochemical studies employing a VDR-specific monoclonal antibody demonstrate that mutation or deletion of this basic domain dramatically attenuates hVDR nuclear localization in transfected COS-7 cells. Although wild-type hVDR is partitioned predominantly to the nucleus in the absence of the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) hormone, treatment with ligand further enhances nuclear translocation, as it does to some degree in receptors with the basic region altered. The role of 1,25(OH)2D3 may be to facilitate hVDR heterodimerization with retinoid X receptors, stimulating subsequent DNA binding and ultimately enhancing nuclear retention. Taken together, these data reveal that the region of hVDR between Arg-49 and Lys-55 contains a novel constitutive nuclear localization signal, RRSMKRK.

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Section: Conserved Basic Amino Acid Sequences Among the Nuclear Proteinsmentioning

confidence: 99%

Novel nuclear localization signal between the two DNA-binding zinc fingers in the human vitamin D receptor

et al. 1998

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“…Vitamin D receptors are present in the crypts of CD intestine, and it is unclear whether the intestinal infl ammation of CD leads to malabsorption of fat-soluble vitamins, and consequent vitamin D defi ciency (12) . Vitamin D defi ciency has been reported in related autoimmune diseases, such as type 1 diabetes mellitus and chronic lymphocytic thyroiditis (13,14) , which are frequently seen in patients with CD (14) .…”

Section: Introductionmentioning

confidence: 99%

Is vitamin D deficiency a feature of pediatric celiac disease?

Villanueva

Maranda

Nwosu

2012

Journal of Pediatric Endocrinology and Metabolism

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Background: Celiac disease (CD) is an autoimmune enteropathy characterized by villus atrophy and malabsorption of essential nutrients. Vitamin D defi ciency has been described in autoimmune diseases, but its status in prepubertal children with CD has not been adequately studied. Objective: To determine the vitamin D status of prepubertal children with CD. Study design: A retrospective study of prepubertal children aged 3 -12 years with CD (n = 24) who were compared to prepubertal, non-CD children of the same age (n = 50). Children were included in the study if they had a diagnosis of CD by intestinal biopsy, and were not on a gluten-free diet (GFD). Patients were excluded if they had diseases of calcium or vitamin D metabolism, or were receiving calcium or vitamin D supplementation or had other autoimmune diseases. All subjects had their serum 25-hydroxyvitamin D [25(OH)D] level measured. Results: There was no difference in 25(OH)D level between the CD and non-CD children (27.58 ± 9.91 vs. 26.20 ± 10.45, p = 0.59). However, when the patients were subdivided into obese and non-obese groups, the non-obese CD patients had a signifi cantly higher 25(OH)D level than the obese normal children (28.39 ± 10.26 vs. 21.58 ± 5.67, p = 0.009). In contrast, there was no difference in 25(OH)D level between non-obese CD patients and non-obese normal children (28.39 ± 10.26 vs. 30.64 ± 12.08, p = 0.52). The season of 25(OH)D measurement was not a signifi cant confounder (p = 0.7). Conclusions: Our data showed no difference in 25(OH) D levels between normal children and those with CD when adjusted for body mass index.

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“…Untreated celiac patients may have low IGF-I levels and the zinc deficiency has been suggested as its cause (18). Vitamin D is also deficient among CD patients despite the fact that diet only provides 5-10% of required vitamin D (20,21), with the rest being achieved from sunlight exposure. No changes in the expression of vitamin D receptors have been detected in this population (22).…”

Section: Discussionmentioning

confidence: 99%

Impact of a gluten-free diet on bone mineral density in celiac patients

Kotze¹,

Skare²,

Vinholi³

et al. 2015

Rev Esp Enferm Dig

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Background: Osteoporosis (OP) is a metabolic bone illness that may complicate celiac disease (CD). It can lead to devastating consequences because of low bone mass and fragility fractures.Purpose: To study the OP prevalence in a group of Brazilian patients with CD and the value of a gluten free diet (GFD).Methods: Retrospective study of celiac female patients from a single University Center followed with bone densitometries. Results from densitometry made at first visit were compared with a second study after a median time of 5 years. During this period, patients were submitted to a GFD according to orientations from special program training. Calcium and vitamin D were prescribed to those patients who did not reach the minimal daily requirement through diet.Results: Forty-one celiac female patients, mean age 46.1 ± 14.8 years, were included. The prevalence of osteopenia at first visit was 56.1% and that of osteoporosis 29.2%. Osteoporosis was associated with longer disease duration (p = 0.01). The second densitometry was performed in a median time of 5 years (range 1 to 13 years) and disclosed 58.9% osteopenia and 28.2% osteoporosis. The GFD improved bone mass, mainly at (of) spine (comparison of T score with p = 0.03 and of bone mass in g/cm

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Localisation of vitamin D receptor in normal human duodenum and in patients with coeliac disease.

Cited by 58 publications

References 26 publications

Novel nuclear localization signal between the two DNA-binding zinc fingers in the human vitamin D receptor

Novel nuclear localization signal between the two DNA-binding zinc fingers in the human vitamin D receptor

Is vitamin D deficiency a feature of pediatric celiac disease?

Impact of a gluten-free diet on bone mineral density in celiac patients

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