Vitamin D receptor is essential for normal keratinocyte stem cell function

The major physiological role of the vitamin D receptor (VDR) is the maintenance of mineral ion homeostasis. Mutation of the VDR, in humans and mice, results in alopecia. Unlike the effects of the VDR on mineral ion homeostasis, the actions of the VDR that prevent alopecia are ligand-independent. Alt...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2007-05, Vol.104 (22), p.9428-9433
Main Authors: Cianferotti, Luisella, Cox, Megan, Skorija, Kristi, Demay, Marie B
Format: Article
Language:English
Subjects:
Alopecia
Animals
Antigens, CD34 - metabolism
beta Catenin - metabolism
Biochemistry
Biological Sciences
Cells, Cultured
Cercopithecus aethiops
COS cells
Hair
Hair Follicle - metabolism
Hair follicles
Keratinocytes
Keratinocytes - cytology
Ligands
Mice
Mice, Knockout
Mutation
Receptors
Receptors, Calcitriol - deficiency
Receptors, Calcitriol - genetics
Receptors, Calcitriol - metabolism
Signal transduction
Stem cells
Stem Cells - metabolism
Transcriptional Activation - genetics
Transgenes
Vitamin D
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The major physiological role of the vitamin D receptor (VDR) is the maintenance of mineral ion homeostasis. Mutation of the VDR, in humans and mice, results in alopecia. Unlike the effects of the VDR on mineral ion homeostasis, the actions of the VDR that prevent alopecia are ligand-independent. Although absence of the VDR does not prevent the development of a keratinocyte stem cell niche in the bulge region of the hair follicle, it results in an inability of these stem cells to regenerate the lower portion of the hair follicle in vivo and impairs keratinocyte stem cell colony formation in vitro. VDR ablation is associated with a gradual decrease in keratinocyte stem cells, accompanied by an increase in sebaceous activity, a phenotype analogous to that seen with impaired canonical Wnt signaling. Transient gene expression assays demonstrate that the cooperative transcriptional effects of β-catenin and Lef1 are abolished in keratinocytes isolated from VDR-null mice, revealing a role for the unliganded VDR in canonical Wnt signaling. Thus, absence of the VDR impairs canonical Wnt signaling in keratinocytes and leads to the development of alopecia due to a defect in keratinocyte stem cells.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0702884104