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Combined Deletion of the Vitamin D Receptor and Calcium-Sensing Receptor Delays Wound Re-epithelialization.
- Source :
-
Endocrinology [Endocrinology] 2017 Jun 01; Vol. 158 (6), pp. 1929-1938. - Publication Year :
- 2017
-
Abstract
- When the skin is injured, keratinocytes proliferate, migrate, and differentiate to regenerate the epidermis. We recently showed that ablation of the vitamin D receptor (Vdr) in keratinocytes delays wound re-epithelialization in mice also fed a low-calcium diet, implicating a cooperative role of Vdr and calcium signaling in this process. In this study, we examined the role of vitamin D and calcium signaling in wound healing by deleting their receptors, Vdr and the calcium-sensing receptor (Casr). Gene expression profiling of neonatal epidermis lacking both Vdr and Casr [Vdr and Casr double knockout (DKO)] specifically in keratinocytes revealed that DKO affects a number of pathways relevant to wound healing, including Vdr, β-catenin, and adherens junction (AJ) signaling. In adult skin, DKO caused a significant delay in wound closure and re-epithelialization, whereas myofibroblast numbers and matrix deposition were unaffected. The injury-induced proliferation of epidermal keratinocytes was blunted in both epidermis and hair follicles, and expression of β-catenin target genes was reduced in the DKO. Expression of E-cadherin and desmoglein 1 was reduced in the shortened leading edges of the epithelial tongues re-epithelializing the wounds, consistent with the decreased migration rate of DKO keratinocytes in vitro. These results demonstrate that Vdr and Casr are required for β-catenin-regulated cell proliferation and AJ formation essential for re-epithelialization after wounding. We conclude that vitamin D and calcium signaling in keratinocytes are required for a normal regenerative response of the skin to wounding.<br /> (Copyright © 2017 Endocrine Society.)
- Subjects :
- Animals
Animals, Newborn
Calcium Signaling genetics
Cell Movement genetics
Cell Proliferation genetics
Cells, Cultured
Humans
Keratinocytes physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Calcium-Sensing
Skin metabolism
Skin physiopathology
Time Factors
beta Catenin metabolism
Re-Epithelialization genetics
Receptors, Calcitriol genetics
Receptors, G-Protein-Coupled genetics
Wound Healing genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 158
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 28368538
- Full Text :
- https://doi.org/10.1210/en.2017-00061