scholarly journals Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 973
Author(s):  
Laura Gisbert-Ferrándiz ◽  
Jesús Cosín-Roger ◽  
Carlos Hernández ◽  
Dulce C. Macias-Ceja ◽  
Dolores Ortiz-Masiá ◽  
...  
Keyword(s):  
Vitamin D ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Vitamin D Receptor ◽  
Receptor Protein ◽  
Intestinal Fibrosis ◽  
Protein Levels ◽  
Therapeutic Value ◽  
Mechanistic Basis

Vitamin D (VD) deficiency has been associated to Crohn’s disease (CD) pathogenesis, and the exogenous administration of VD improves the course of the disease, but the mechanistic basis of these observations remains unknown. Vitamin D receptor (VDR) mediates most of the biological functions of this hormone, and we aim to analyze here the expression of VDR in intestinal tissue, epithelial cells, and fibroblasts from CD patients. The effects of VD on a fibroblast wound healing assay and murine intestinal fibrosis are also analyzed. Our data show diminished VDR protein levels in surgical resections and epithelial cells from CD patients. In intestinal fibroblasts isolated from damaged tissue of CD patients, we detected enhanced migration and decreased VDR expression compared with both fibroblasts from non-damaged tissue of the same CD patient or control fibroblasts. Treatment with VD increased VDR protein levels, avoided the accelerated migration in CD fibroblasts, and prevented murine intestinal fibrosis induced by the heterotopic transplant model. In conclusion, our study demonstrates diminished VDR protein levels associated with enhanced migration in intestinal fibroblasts from damaged tissue of CD patients. In these cells, VD accumulates VDR and normalizes migration, which supports that CD patients would benefit from the VD anti-fibrotic therapeutic value that we demonstrate in a murine experimental model.

scholarly journals P649 Relationship between clinical characteristics and vitamin D receptor polymorphisms in Crohn's disease

2014 ◽  
Vol 8 ◽  
pp. S341
Author(s):  
O. Terjek ◽  
A.A. Csontos ◽  
K. Lorinczy ◽  
A. Bors ◽  
A. Torday ◽  
...  
Keyword(s):  
Vitamin D ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Vitamin D Receptor ◽  
Clinical Characteristics

scholarly journals Flow cytometry detection of vitamin D receptor changes during vitamin D treatment in Crohn's disease

2015 ◽  
Vol 181 (1) ◽  
pp. 19-28 ◽  
Author(s):  
M. Bendix ◽  
A. Dige ◽  
B. Deleuran ◽  
J. F. Dahlerup ◽  
S. P. Jørgensen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Flow Cytometry ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Vitamin D Receptor ◽  
Flow Cytometry Detection

scholarly journals A Single Nucleotide Polymorphism in the Vitamin D Receptor Gene Is Associated With Decreased Levels of the Protein and a Penetrating Pattern in Crohn’s Disease

2018 ◽  
Vol 24 (7) ◽  
pp. 1462-1470 ◽  
Author(s):  
Laura Gisbert-Ferrándiz ◽  
Pedro Salvador ◽  
Dolores Ortiz-Masiá ◽  
Dulce Carolina Macías-Ceja ◽  
Samuel Orden ◽  
...  
Keyword(s):  
Vitamin D ◽  
Single Nucleotide Polymorphism ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Vitamin D Receptor ◽  
Receptor Gene ◽  
Vitamin D Receptor Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

scholarly journals Herbs-Partitioned Moxibustion Combined with Acupuncture Inhibits TGF-β1-Smad-Snail-Induced Intestinal Epithelial Mesenchymal Transition in Crohn’s Disease Model Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yin Shi ◽  
Tao Li ◽  
Jing Zhou ◽  
Yuwei Li ◽  
Liu Chen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Intestinal Epithelial Cells ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Cell Marker ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis

Crohn’s disease may cause excessive damage and repair in the intestinal epithelium due to its chronic relapsing intestinal inflammation. These factors may initiate the TGF-β 1-Smad pathway to activate the transcription factor of Snail, and the Snail-mediated pathway promotes the transformation of intestinal epithelial cells to mesenchymal cells, leading to intestinal fibrosis. Acupuncture and moxibustion have been demonstrated to prevent intestinal fibrosis in Crohn’s disease. However, it is not clear whether acupuncture and moxibustion can inhibit intestinal epithelial mesenchymal transformation in Crohn’s disease by affecting the TGF-β 1-Smad-Snail pathway. This study indicated that abnormal increased expressions of TGFβ1, TβR2, Smad3, and Snail were significantly downregulated by herbs-partitioned moxibustion at Tianshu (ST25) and Qihai (RN6) and acupuncture at Zusanli (ST36) and Shangjuxu (ST37). In addition, protein and mRNA levels of E-cadherin, the epithelial cell marker, were significantly increased. Protein and mRNA levels of fibronectin, the mesenchymal cell marker, were decreased in the intestinal tissue. Moreover, the number of mesenchymal cells in the intestinal mucosa can be reversely transformed to intestinal epithelial cells. Therefore, herbs-partitioned moxibustion combined with acupuncture can prevent intestinal epithelial mesenchymal transition by inhibiting abnormal expression of TGFβ1, TβR2, Smad3, and Snail in the TGF-β1-Smad-Snail pathway in Crohn’s disease.

P045 Local inflammation modulates vitamin D receptor protein levels in fibroblasts

2019 ◽  
Vol 13 (Supplement_1) ◽  
pp. S109-S109
Author(s):  
L Gisbert-Ferrándiz ◽  
J Cosin-Roger ◽  
P Salvador ◽  
D C Macias-Ceja ◽  
F Navarro-Vicente ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Receptor Protein ◽  
Local Inflammation ◽  
Protein Levels

scholarly journals Vitamin D and Inflammatory Bowel Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Marco Ardesia ◽  
Guido Ferlazzo ◽  
Walter Fries
Keyword(s):  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Vitamin D Receptor ◽  
Bowel Disease ◽  
Vitamin D Levels ◽  
Inflammatory Bowel ◽  
Low Serum

Vitamin D deficiency has been recognized as an environmental risk factor for Crohn’s disease since the early 80s. Initially, this finding was correlated with metabolic bone disease. Low serum 25-hydroxyvitamin D levels have been repeatedly reported in inflammatory bowel diseases together with a relationship between vitamin D status and disease activity. Subsequently, low serum vitamin D levels have been reported in various immune-related diseases pointing to an immunoregulatory role. Indeed, vitamin D and its receptor (VDR) are known to interact with different players of the immune homeostasis by controlling cell proliferation, antigen receptor signalling, and intestinal barrier function. Moreover, 1,25-dihydroxyvitamin D is implicated in NOD2-mediated expression of defensin-β2, the latter known to play a crucial role in the pathogenesis of Crohn’s disease (IBD1 gene), and several genetic variants of the vitamin D receptor have been identified as Crohn’s disease candidate susceptibility genes. From animal models we have learned that deletion of the VDR gene was associated with a more severe disease. There is a growing body of evidence concerning the therapeutic role of vitamin D/synthetic vitamin D receptor agonists in clinical and experimental models of inflammatory bowel disease far beyond the role of calcium homeostasis and bone metabolism.

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