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

Hengguang Zhao, Sandra Rieger, Koichiro Abe, Martin Hewison, Thomas S. Lisse

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1984
JournalInternational journal of molecular sciences
Volume17
Issue number12
DOIs
StatePublished - Dec 2016
Externally publishedYes

Keywords

  • DDIT4
  • Hair follicle
  • mTOR
  • Stem cells
  • Stress
  • VDR
  • Wound repair

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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