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DNA Damage-Inducible Transcript 4 Is an Innate Surveillant of Hair Follicular Stress in Vitamin D Receptor Knockout Mice and a Regulator of Wound Re-Epithelialization

1
Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
2
Kathryn W. Davis Center for Regenerative Biology and Medicine, Mount Desert Island Biological Laboratory, 159 Old Bar Harbor Road, Salisbury Cove, ME 04672, USA
3
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
4
Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, The University of Birmingham, Birmingham B15 2TH, UK
5
The Jackson Laboratory, Bar Harbor, ME 04609, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Allison Cowin
Int. J. Mol. Sci. 2016, 17(12), 1984; https://doi.org/10.3390/ijms17121984
Received: 19 October 2016 / Revised: 7 November 2016 / Accepted: 22 November 2016 / Published: 26 November 2016
(This article belongs to the Special Issue Wound Repair and Regeneration)
Mice and human patients with impaired vitamin D receptor (VDR) signaling have normal developmental hair growth but display aberrant post-morphogenic hair cycle progression associated with alopecia. In addition, VDR–/– mice exhibit impaired cutaneous wound healing. We undertook experiments to determine whether the stress-inducible regulator of energy homeostasis, DNA damage-inducible transcript 4 (Ddit4), is involved in these processes. By analyzing hair cycle activation in vivo, we show that VDR−/− mice at day 14 exhibit increased Ddit4 expression within follicular stress compartments. At day 29, degenerating VDR−/− follicular keratinocytes, but not bulge stem cells, continue to exhibit an increase in Ddit4 expression. At day 47, when normal follicles and epidermis are quiescent and enriched for Ddit4, VDR−/− skin lacks Ddit4 expression. In a skin wound healing assay, the re-epithelialized epidermis in wildtype (WT) but not VDR−/− animals harbor a population of Ddit4- and Krt10-positive cells. Our study suggests that VDR regulates Ddit4 expression during epidermal homeostasis and the wound healing process, while elevated Ddit4 represents an early growth-arresting stress response within VDR−/− follicles. View Full-Text
Keywords: wound repair; VDR; mTOR; DDIT4; stress; hair follicle; stem cells wound repair; VDR; mTOR; DDIT4; stress; hair follicle; stem cells
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MDPI and ACS Style

Zhao, H.; Rieger, S.; Abe, K.; Hewison, M.; Lisse, T.S. DNA Damage-Inducible Transcript 4 Is an Innate Surveillant of Hair Follicular Stress in Vitamin D Receptor Knockout Mice and a Regulator of Wound Re-Epithelialization. Int. J. Mol. Sci. 2016, 17, 1984. https://doi.org/10.3390/ijms17121984

AMA Style

Zhao H, Rieger S, Abe K, Hewison M, Lisse TS. DNA Damage-Inducible Transcript 4 Is an Innate Surveillant of Hair Follicular Stress in Vitamin D Receptor Knockout Mice and a Regulator of Wound Re-Epithelialization. International Journal of Molecular Sciences. 2016; 17(12):1984. https://doi.org/10.3390/ijms17121984

Chicago/Turabian Style

Zhao, Hengguang; Rieger, Sandra; Abe, Koichiro; Hewison, Martin; Lisse, Thomas S. 2016. "DNA Damage-Inducible Transcript 4 Is an Innate Surveillant of Hair Follicular Stress in Vitamin D Receptor Knockout Mice and a Regulator of Wound Re-Epithelialization" Int. J. Mol. Sci. 17, no. 12: 1984. https://doi.org/10.3390/ijms17121984

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Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

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