Department of Burn Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China.
Department of Burn Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
Biosci Rep. 2016 Aug 5;36(4). doi: 10.1042/BSR20160034. Print 2016 Aug.
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.
慢性、难以愈合的伤口是糖尿病的主要并发症。最近，已有多种细胞疗法被报道可促进糖尿病伤口愈合。表皮干细胞（ESC）被认为是组织治疗的有力工具。然而，ESC 在糖尿病伤口愈合中的治疗特性的作用和机制尚不清楚。在此，为了确定 ESC 促进糖尿病伤口愈合的能力，我们使用链脲佐菌素（STZ）诱导的糖尿病（DM）小鼠模型中的背部皮肤缺损。从鼠皮中分离出 ESC。我们发现，在伤口边缘，Notch 配体 Jagged1（Jag1）、Notch1 和 Notch 靶基因 Hairy Enhancer of Split-1（Hes1）的 mRNA 和蛋白水平均显著升高。此外，我们观察到 Jag1 在 ESC 中高表达。Jag1 的过表达促进 ESC 迁移，而 Jag1 的敲低则导致 ESC 迁移在体外显著减少。重要的是，Jag1 的过表达可改善体内糖尿病伤口愈合。这些结果提供了证据表明，ESC 通过 Notch 信号通路加速糖尿病伤口愈合，并为激活 Notch 通路治疗糖尿病伤口提供了有前景的潜力。
