Combined Deletion of the Vitamin D Receptor and Calcium-Sensing Receptor Delays Wound Re-epithelialization
Combined Deletion of the Vitamin D Receptor and Calcium-Sensing Receptor Delays Wound Re-epithelialization
复制标题
维生素 D 受体和钙敏感受体的联合缺失会延迟伤口上皮再生
DOI：
10.1210/en.2017-00061
复制
发表时间：
2017-06-01
期刊：
影响因子：
4.8
通讯作者：
Bikle, Daniel D.
中科院分区：
文献类型：
--
作者：
Oda, Yuko;Hu, Lizhi;Bikle, Daniel D.
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.
