title: Vitamin D receptor knockout mice exhibit elongated intestinal microvilli and increased ezrin expression.
abstract: In addition to its principle function as a calcium regulator, vitamin D can affect cell and tissue morphology. The intestine is an important target tissue of vitamin D, as it must ensure the efficient transport of nutrients across the epithelium while excluding the passage of harmful molecules and bacteria into the organism. These functions require a highly organized morphology, which may be modified by vitamin D deficiency. To elucidate the role of vitamin D in gut morphology and barrier function, we compared the enterocyte microstructures, gut permeability, and cytoskeletal and cell junction protein expression in vitamin D receptor (VDR) knockout (KO) and wild-type (WT) mice. We found that the duodenal epithelial cells in the VDR-KO mice had longer microvilli (+19%) than those of the WT mice (P < .05). Interestingly, microvilli elongation in the VDR-KO mice was associated with higher messenger RNA and protein expression of ezrin, which is involved in the regulation of microvillus morphogenesis. Intestinal tight junction width and permeability were assessed by measuring the fluorescein isothiocyanate dextran concentrations in plasma; the concentrations were comparable between the 2 groups of mice. We further observed a decrease in the messenger RNA and protein expression of the calcium-transporting tight junction protein claudin-2 in the VDR-KO mice compared with the WT mice (P < .05). In conclusion, the mice lacking VDR had longer enterocyte microvilli, likely as a result of increased ezrin expression. However, the morphology of the tight junctions and the intestinal permeability for large molecules were not affected.
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany. Electronic address: hagen.kuehne@landw.uni-halle.de.
authors.forename: Hagen
authors.initials: H
authors.lastname: Kühne
authors.affiliation: Biocenter of the Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany. Electronic address: gerd.hause@biozentrum.uni-halle.de.
authors.forename: Gerd
authors.initials: G
authors.lastname: Hause
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany. Electronic address: sarah.grundmann@landw.uni-halle.de.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Grundmann
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany. Electronic address: alexandra.schutkowski@landw.uni-halle.de.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schutkowski
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany. Electronic address: corinna.brandsch@landw.uni-halle.de.
authors.forename: Corinna
authors.initials: C
authors.lastname: Brandsch
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany. Electronic address: gabriele.stangl@landw.uni-halle.de.
authors.forename: Gabriele I
authors.initials: GI
authors.lastname: Stangl
mesh_terms: D000818:Animals; D002762:Cholecalciferol / Q000627:therapeutic use; D062446:Claudin-2 / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation; D007408:Intestinal Absorption; D008297:Male; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008871:Microvilli / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure; D014808:Vitamin D Deficiency / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology; D000099149:Ezrin
chemical_list: D002762:Cholecalciferol; D062446:Claudin-2; D003598:Cytoskeletal Proteins; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D000099149:Ezrin; C015219:fluorescein isothiocyanate dextran
keywords: Ezrin; Gut permeability; Intestine; Microvilli; Mouse; Vitamin D receptor