| First Author | Zhao H | Year | 2016 |
| Journal | Int J Mol Sci | Volume | 17 |
| Issue | 12 | PubMed ID | 27898044 |
| Mgi Jnum | J:312642 | Mgi Id | MGI:6791875 |
| Doi | 10.3390/ijms17121984 | Citation | Zhao H, et al. (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(12):1984 |
| abstractText | 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. |
