Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Department of Plastic and Reconstructive Surgery, Yeungnam University College of Medicine, Daegu, Republic of Korea.
Adv Wound Care (New Rochelle). 2020 Nov;9(11):591-601. doi: 10.1089/wound.2019.1015. Epub 2019 Dec 12.
This study aimed to elucidate the role of the proangiogenic transcription factors Sox7 and Sox17 in the wound healing process and investigate the therapeutic potential of Dll4 blockade, which is an upstream regulator of Sox17, for the treatment of nonhealing wounds. After generating a full-thickness skin defect wound model of endothelial Sox7- and/or Sox17-deficient mice, we measured the wound healing rates and performed histological analysis. The effects of an anti-Dll4 antibody on wound angiogenesis in -deficient mice and diabetic mice were assessed. Sox7 and/or Sox17 deletion delayed wound healing. Moreover, the loss of Sox7 and Sox17 inhibited wound angiogenesis, without affecting the expression of the other. Of interest, after anti-Dll4 antibody treatment, Sox17 levels were increased and the suppression of angiogenesis was alleviated in -deficient mice and diabetic mice. Consequently, Dll4 blockade effectively recovered the observed delay in wound healing. The proangiogenic role of Sox7 and Sox17 in wound angiogenesis was addressed and effective treatment of nonhealing wounds by Dll4 blockade was suggested. This study revealed the proangiogenic role of the transcription factors Sox7 and Sox17 in wound angiogenesis. Furthermore, we suggest a novel method for treating nonhealing wounds by particularly targeting the Dll4-Sox17 axis.
本研究旨在阐明促血管生成转录因子 Sox7 和 Sox17 在伤口愈合过程中的作用，并研究 Dll4 阻断（Sox17 的上游调节剂）治疗非愈合性伤口的治疗潜力。 在生成内皮 Sox7-和/或 Sox17 缺陷型小鼠的全层皮肤缺损伤口模型后，我们测量了伤口愈合率并进行了组织学分析。评估了抗 Dll4 抗体对 -缺陷型小鼠和糖尿病小鼠伤口血管生成的影响。 Sox7 和/或 Sox17 的缺失延迟了伤口愈合。此外，Sox7 和 Sox17 的缺失抑制了伤口血管生成，而不影响其他的表达。有趣的是，在用抗 Dll4 抗体治疗后，Sox17 水平在 -缺陷型小鼠和糖尿病小鼠中增加，并且血管生成的抑制作用得到缓解。因此，Dll4 阻断有效地恢复了观察到的伤口愈合延迟。 本研究探讨了 Sox7 和 Sox17 在伤口血管生成中的促血管生成作用，并提出了通过 Dll4 阻断有效治疗非愈合性伤口的方法。 这项研究揭示了转录因子 Sox7 和 Sox17 在伤口血管生成中的促血管生成作用。此外，我们建议通过特别针对 Dll4-Sox17 轴来治疗非愈合性伤口的新方法。
