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Open Access Highly Accessed Research

Vitamin D receptor regulates intestinal proteins involved in cell proliferation, migration and stress response

Hagen Kühne1, Alexandra Schutkowski1, Susann Weinholz2, Christina Cordes2, Angelika Schierhorn3, Kristin Schulz4, Bettina König1 and Gabriele I Stangl1*

Author Affiliations

1 Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Von-Danckelmann-Platz 2, D-06120 Halle (Saale), Germany

2 Department of Applied Biosciences and Process Engineering, Anhalt University of Applied Sciences, D-06366 Köthen, Germany

3 Institute for Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, D-06120 Halle (Saale), Germany

4 Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, D-06112 Halle (Saale), Germany

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Lipids in Health and Disease 2014, 13:51  doi:10.1186/1476-511X-13-51

Published: 19 March 2014

Abstract

Background

Genome-wide association studies found low plasma levels of 25-hydroxyvitamin D and vitamin D receptor (VDR) polymorphisms associated with a higher prevalence of pathological changes in the intestine such as chronic inflammatory bowel diseases.

Methods

In this study, a proteomic approach was applied to understand the overall physiological importance of vitamin D in the small intestine, beyond its function in calcium and phosphate absorption.

Results

In total, 569 protein spots could be detected by two-dimensional-difference in-gel electrophoresis (2D-DIGE), and 82 proteins were considered as differentially regulated in the intestinal mucosa of VDR-deficient mice compared to that of wildtype (WT) mice. Fourteen clearly detectable proteins were identified by MS/MS and further analyzed by western blot and/or real-time RT-PCR. The differentially expressed proteins are functionally involved in cell proliferation, cell adhesion and cell migration, stress response and lipid transport. Mice lacking VDR revealed higher levels of intestinal proteins associated with proliferation and migration such as the 37/67 kDa laminin receptor, collagen type VI (alpha 1 chain), keratin-19, tropomyosin-3, adseverin and higher levels of proteins involved in protein trafficking and stress response than WT mice. In contrast, proteins that are involved in transport of bile and fatty acids were down-regulated in small intestine of mice lacking VDR compared to WT mice. However, plasma and liver concentrations of cholesterol and triglycerides were not different between the two groups of mice.

Conclusion

Collectively, these data imply VDR as an important factor for controlling cell proliferation, migration and stress response in the small intestine.

Keywords:
VDR-deficiency; Small intestine; Proteomics; Laminin receptor; Cell adhesion; Mice; Stress response