Analysis of 1,25-Dihydroxyvitamin D 3 Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids

Author:

Li Shanshan1,De La Cruz Jessica1,Hutchens Steven2,Mukhopadhyay Somshuvra2,Criss Zachary K.3,Aita Rohit4,Pellon-Cardenas Oscar4,Hur Joseph4,Soteropoulos Patricia15,Husain Seema15,Dhawan Puneet15,Verlinden Lieve6,Carmeliet Geert6,Fleet James C.7,Shroyer Noah F.3,Verzi Michael P.4,Christakos Sylvia1ORCID

Affiliation:

1. Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA

2. Division of Pharmacology and Toxicology, College of Pharmacy, Institute for Cellular and Molecular Biology and Institute for Neuroscience, The University of Texas at Austin, Austin, Texas, USA

3. Integrative Molecular and Biomedical Sciences Graduate Program, Division of Medicine, Baylor College of Medicine, Houston, Texas, USA

4. Department of Genetics, Rutgers University, New Brunswick, New Jersey, USA

5. Genomics Center, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA

6. Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, Leuven, Belgium

7. Department of Nutrition Science, Purdue University, West Lafayette, Indiana, USA

Abstract

Although vitamin D is critical for the function of the intestine, most studies have focused on the duodenum. We show that transgenic expression of the vitamin D receptor (VDR) only in the distal intestine of VDR null mice (KO/TG mice) results in the normalization of serum calcium and rescue of rickets. Although it had been suggested that calcium transport in the distal intestine involves a paracellular process, we found that the 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]-activated genes in the proximal intestine associated with active calcium transport ( Trpv6 , S100g , and Atp2b1 ) are also induced by 1,25(OH) 2 D 3 in the distal intestine of KO/TG mice.

Funder

National Institutes of Health

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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