Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway.
Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway.
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表皮干细胞 (ESC) 通过 Notch 信号通路加速糖尿病伤口愈合。
DOI：
10.1042/bsr20160034
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发表时间：
2016-08
影响因子：
4
通讯作者：
Xie JL
中科院分区：
文献类型：
--
作者：
Yang RH;Qi SH;Shu B;Ruan SB;Lin ZP;Lin Y;Shen R;Zhang FG;Chen XD;Xie JL
表皮干细胞（ESC）通过Notch信号通路加速糖尿病伤口愈合。慢性、不愈合的伤口是糖尿病的主要并发症。最近，已经报道了用于促进糖尿病伤口愈合的各种细胞疗法。表皮干细胞（ESCs）被认为是组织治疗的有力工具。然而，ESCs在糖尿病创面愈合中的作用及其机制尚不清楚。本文中，为了确定ESC对糖尿病伤口愈合的能力，使用链脲佐菌素（STZ）诱导的糖尿病（DM）小鼠模型中的背部皮肤缺损。从小鼠皮肤分离ESC。我们发现Notch配体Jagged 1（Jag 1）、Notch 1和Notch靶基因Hairy Enhancer of Split-1（Hes 1）的mRNA和蛋白水平在伤口边缘显著增加。此外，我们观察到Jag 1在ESCs中高表达。Jag 1的过表达促进了ESCs的迁移，而敲低Jag 1则导致了ESCs体外迁移的显著减少。重要的是，Jag 1过表达改善体内糖尿病伤口愈合。这些结果提供了ESCs通过Notch信号通路加速糖尿病伤口愈合的证据，并提供了激活Notch通路用于治疗糖尿病伤口的有希望的潜力。
Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway. Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro. Importantly, Jag1 overexpression improves diabetic wound healing in vivo. These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound.