Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Australia.
Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Australia.
Burns. 2019 May;45(3):682-690. doi: 10.1016/j.burns.2018.10.002. Epub 2018 Oct 25.
Ephrin ligand/Eph receptor signaling is important in both tissue development and homeostasis. There is increasing evidence that Ephrin/Eph signaling is important in the skin, involved in hair follicle cycling, epidermal differentiation, cutaneous innervation and skin cancer. However, there is currently limited information on the role of Ephrin/Eph signaling in cutaneous wound healing. Here we report the effects of the Ephrin-A2 and A5 ligands on wound healing. Using Ephrin-A2, Ephrin-A5 and Ephrin-A2A5 transgenic mice, in vitro wound healing assays were conducted using isolated keratinocytes and fibroblasts. Ephrin-A2, Ephrin-A2A5 and wild type mice with excisional wounds were used to analyze the impact of these ligands on wound closure, scar outcome, collagen orientation and re-innervation in vivo. The absence of the Ephrin-A2 and A5 ligands did not have any effect on dermal fibroblast proliferation or on fibroblast or keratinocyte migration. The loss of Ephrin-A2 and A5 ligands did not impact on the rate of wound closure or re-innervation after injury. However, changes in the gross morphology of the healed scar and in collagen histology of the scar dermis were observed in transgenic mice. Therefore Ephrin-A2 and A5 ligands may play an important role in final scar appearance associated with collagen deposition and structure.
Ephrin 配体/Eph 受体信号在组织发育和稳态中都很重要。越来越多的证据表明 Ephrin/Eph 信号在皮肤中很重要，参与毛囊周期、表皮分化、皮肤神经支配和皮肤癌。然而，目前关于 Ephrin/Eph 信号在皮肤创伤愈合中的作用的信息有限。在这里，我们报告了 Ephrin-A2 和 A5 配体对创伤愈合的影响。使用 Ephrin-A2、Ephrin-A5 和 Ephrin-A2A5 转基因小鼠，通过分离的角质形成细胞和成纤维细胞进行体外伤口愈合测定。使用 Ephrin-A2、Ephrin-A2A5 和野生型小鼠进行切除性伤口，分析这些配体对体内伤口闭合、疤痕结果、胶原取向和再神经支配的影响。Ephrin-A2 和 A5 配体的缺失对真皮成纤维细胞的增殖或成纤维细胞或角质形成细胞的迁移没有任何影响。Ephrin-A2 和 A5 配体的缺失不影响损伤后伤口闭合或再神经支配的速度。然而，在转基因小鼠中观察到愈合疤痕的大体形态和疤痕真皮胶原组织学的变化。因此，Ephrin-A2 和 A5 配体可能在与胶原沉积和结构相关的最终疤痕外观中发挥重要作用。
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