title: Role of the sodium-dependent multivitamin transporter (SMVT) in the maintenance of intestinal mucosal integrity.
abstract: Utilizing a conditional (intestinal-specific) knockout (cKO) mouse model, we have recently shown that the sodium-dependent multivitamin transporter (SMVT) (SLC5A6) is the only biotin uptake system that operates in the gut and that its deletion leads to biotin deficiency. Unexpectedly, we also observed that all SMVT-cKO mice develop chronic active inflammation, especially in the cecum. Our aim here was to examine the role of SMVT in the maintenance of intestinal mucosal integrity [permeability and expression of tight junction (TJ) proteins]. Our results showed that knocking out the mouse intestinal SMVT is associated with a significant increase in gut permeability and with changes in the level of expression of TJ proteins. To determine whether these changes are related to the state of biotin deficiency that develops in SMVT-cKO mice, we induced (by dietary means) biotin deficiency in wild-type mice and examined its effect on the above-mentioned parameters. The results showed that dietary-induced biotin deficiency leads to a similar development of chronic active inflammation in the cecum with an increase in the level of expression of proinflammatory cytokines, as well as an increase in intestinal permeability and changes in the level of expression of TJ proteins. We also examined the effect of chronic biotin deficiency on permeability and expression of TJ proteins in confluent intestinal epithelial Caco-2 monolayers but observed no changes in these parameters. These results show that the intestinal SMVT plays an important role in the maintenance of normal mucosal integrity, most likely via its role in providing biotin to different cells of the gut mucosa.
authors: Department of Medical Research, VA Medical Center, Long Beach, California; Departments of Medicine, University of California, Irvine, California; Department of Physiology/Biophysics, University of California, Irvine, California.
authors: Subrata
authors: S
authors: Sabui
authors: Department of Medical Research, VA Medical Center, Long Beach, California; Departments of Medicine, University of California, Irvine, California; Department of Physiology/Biophysics, University of California, Irvine, California.
authors: Jennifer Ann
authors: JA
authors: Bohl
authors: Department of Medical Research, VA Medical Center, Long Beach, California; Departments of Medicine, University of California, Irvine, California; Department of Physiology/Biophysics, University of California, Irvine, California.
authors: Rubina
authors: R
authors: Kapadia
authors: Department of Medical Research, VA Medical Center, Long Beach, California; Departments of Medicine, University of California, Irvine, California; Department of Physiology/Biophysics, University of California, Irvine, California.
authors: Kyle
authors: K
authors: Cogburn
authors: Department of Medical Research, VA Medical Center, Long Beach, California; Departments of Medicine, University of California, Irvine, California; Department of Physiology/Biophysics, University of California, Irvine, California.
authors: Abhisek
authors: A
authors: Ghosal
authors: Department of Medical Research, VA Medical Center, Long Beach, California; Departments of Medicine, University of California, Irvine, California; Department of Physiology/Biophysics, University of California, Irvine, California.
authors: Nils W
authors: NW
authors: Lambrecht
authors: Department of Medical Research, VA Medical Center, Long Beach, California; Departments of Medicine, University of California, Irvine, California; Department of Physiology/Biophysics, University of California, Irvine, California hmsaid@uci.edu.
authors: Hamid M
authors: HM
authors: Said
mesh_terms: D000818:Animals; D001710:Biotin / Q000008:administration & dosage; D028921:Biotinidase Deficiency / Q000378:metabolism; D018938:Caco-2 Cells; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D027981:Symporters; D062725:Tight Junction Proteins; C119981:biotin transporter; D001710:Biotin
keywords: biotin; mucosal inflammation; mucosal integrity; sodium-dependent multivitamin transporter knockout; tight junction proteins