PMID- 28368538
OWN - NLM
STAT- MEDLINE
DCOM- 20170907
LR  - 20191210
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 158
IP  - 6
DP  - 2017 Jun 1
TI  - Combined Deletion of the Vitamin D Receptor and Calcium-Sensing Receptor Delays 
      Wound Re-epithelialization.
PG  - 1929-1938
LID - 10.1210/en.2017-00061 [doi]
AB  - 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, beta-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 beta-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 beta-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.
CI  - Copyright (c) 2017 Endocrine Society.
FAU - Oda, Yuko
AU  - Oda Y
AD  - Department of Medicine, University of California San Francisco, San Francisco, 
      California 94158.
AD  - Department of Dermatology, University of California San Francisco, San Francisco, 
      California 94158.
FAU - Hu, Lizhi
AU  - Hu L
AD  - Department of Medicine, University of California San Francisco, San Francisco, 
      California 94158.
AD  - School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, 
      China.
FAU - Nguyen, Thai
AU  - Nguyen T
AD  - San Francisco Veterans Affairs Medical Center, San Francisco, California 94158.
FAU - Fong, Chak
AU  - Fong C
AD  - San Francisco Veterans Affairs Medical Center, San Francisco, California 94158.
FAU - Tu, Chia-Ling
AU  - Tu CL
AD  - San Francisco Veterans Affairs Medical Center, San Francisco, California 94158.
FAU - Bikle, Daniel D
AU  - Bikle DD
AD  - San Francisco Veterans Affairs Medical Center, San Francisco, California 94158.
LA  - eng
GR  - R01 AR050023/AR/NIAMS NIH HHS/United States
GR  - R01 AR056256/AR/NIAMS NIH HHS/United States
GR  - I01 BX001066/BX/BLRD VA/United States
GR  - R21 DE025357/DE/NIDCR NIH HHS/United States
GR  - I01 BX003814/BX/BLRD VA/United States
PT  - Journal Article
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (CASR protein, mouse)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Calcium Signaling/genetics
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - Cells, Cultured
MH  - Humans
MH  - Keratinocytes/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Re-Epithelialization/*genetics
MH  - Receptors, Calcitriol/*genetics
MH  - Receptors, Calcium-Sensing
MH  - Receptors, G-Protein-Coupled/*genetics
MH  - Skin/metabolism/physiopathology
MH  - Time Factors
MH  - Wound Healing/*genetics
MH  - beta Catenin/metabolism
PMC - PMC5460927
EDAT- 2017/04/04 06:00
MHDA- 2017/09/08 06:00
PMCR- 2018/06/01
CRDT- 2017/04/04 06:00
PHST- 2017/01/13 00:00 [received]
PHST- 2017/03/08 00:00 [accepted]
PHST- 2017/04/04 06:00 [pubmed]
PHST- 2017/09/08 06:00 [medline]
PHST- 2017/04/04 06:00 [entrez]
PHST- 2018/06/01 00:00 [pmc-release]
AID - 3077225 [pii]
AID - endo_201700061 [pii]
AID - 10.1210/en.2017-00061 [doi]
PST - ppublish
SO  - Endocrinology. 2017 Jun 1;158(6):1929-1938. doi: 10.1210/en.2017-00061.