Department of Dermatology, the Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China; Department of Dermatology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Dermatology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
J Dermatol Sci. 2020 Nov;100(2):120-128. doi: 10.1016/j.jdermsci.2020.08.015. Epub 2020 Sep 7.
Wound healing is a complex physiological process that is crucial for reestablishing the epithelial barrier following injury.
The aim of this study was to demonstrate the efficacy of calcipotriol, a synthetic vitamin D3 analogue, in wound healing in an acute mice wound model.
An excision wound model was established in mice, and the wound healing activity of calcipotriol was evaluated. Human keratinocyte cell lines, HaCaT and NHEK, were utilized in in vitro skin wound healing model. Cytokine expression levels were measured by real-time PCR and ELISA assay. The expression of epithelial-mesenchymal transition (EMT)-associated molecules and the phosphorylation of Yes-associated protein (YAP) was determined by western blotting.
The increase in re-epithelialization by calcipotriol treatment early in the wound was associated with the EMT process. A scratch assay using HaCaT and NHEK cells also showed that calcipotriol administration resulted in effective wound closure. We demonstrated that calcipotriol promoted keratinocyte migration by interfering with the Hippo pathway. Calcipotriol-mediated enhancement of cell migration is related to downregulated phosphorylation of YAP and increased levels of YAP and PDZ-binding motif (TAZ). Mechanistically, we defined that calcipotriol facilitated the crosstalk between the YAP/TAZ and TGF-β/Smad signaling pathways, eliciting EMT in keratinocytes during the wound healing process.
These results suggest that the positive effect of calcipotriol on keratinocyte migration is mediated by the induction of EMT via the regulation of Hippo pathway, which promotes the acceleration of wound closure.
伤口愈合是一个复杂的生理过程，对于损伤后重新建立上皮屏障至关重要。
本研究旨在证明合成维生素 D3 类似物卡泊三醇在急性小鼠伤口模型中促进伤口愈合的功效。
建立了小鼠切除伤口模型，并评估了卡泊三醇的伤口愈合活性。利用人角质形成细胞系 HaCaT 和 NHEK 进行体外皮肤伤口愈合模型。通过实时 PCR 和 ELISA 测定细胞因子表达水平。通过 Western blot 测定上皮-间充质转化（EMT）相关分子的表达和 Yes 相关蛋白（YAP）的磷酸化。
卡泊三醇在伤口早期促进再上皮化的增加与 EMT 过程有关。HaCaT 和 NHEK 细胞的划痕实验也表明，卡泊三醇给药可导致有效伤口闭合。我们证明，卡泊三醇通过干扰 Hippo 通路促进角质形成细胞迁移。卡泊三醇介导的细胞迁移增强与 YAP 的磷酸化下调以及 YAP 和 PDZ 结合基序（TAZ）水平增加有关。从机制上讲，我们确定卡泊三醇促进了 YAP/TAZ 和 TGF-β/Smad 信号通路之间的串扰，在伤口愈合过程中诱导角质形成细胞发生 EMT。
这些结果表明，卡泊三醇对角质形成细胞迁移的积极影响是通过调节 Hippo 通路诱导 EMT 介导的，从而促进伤口闭合的加速。
