Antioxidative and Angiogenesis-Promoting Effects of Tetrahedral Framework Nucleic Acids in Diabetic Wound Healing with Activation of the Akt/Nrf2/HO-1 Pathway.,ACS Applied Materials & Interfaces

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Antioxidative and Angiogenesis-Promoting Effects of Tetrahedral Framework Nucleic Acids in Diabetic Wound Healing with Activation of the Akt/Nrf2/HO-1 Pathway.
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-02-21 , DOI: 10.1021/acsami.0c00874
Shiyu Lin ₁ , Qi Zhang ₁ , Songhang Li ₁ , Tao Zhang ₁ , Lang Wang ₂ , Xin Qin ₁ , Mei Zhang ₁ , Sirong Shi ₁ , Xiaoxiao Cai ₁

Affiliation

Currently available strategies show limited effects in preventing morbidity and disability from chronic diabetic wounds. Ideal vascularization is indispensable for better restoration and prognosis of diabetic wounds. This study aims to investigate the role of tetrahedral framework nucleic acids (tFNAs) in the process of angiogenesis during diabetic wound healing and the underlying mechanism. The in vitro results showed that tFNAs treatment enhanced the formation of a vessel-like structure that was inhibited by advanced glycation end products (AGEs). Positive variations were detected in aspects of cell viability, migratory ability, nitric oxide (NO) levels, and vascular endothelial growth factor-A (VEGF-A) expression. In addition, high reactive oxygen species (ROS) levels and gene expressions relevant to oxidative damage and inflammation in diabetic human umbilical vein endothelial cells (HUVECs) were attenuated by tFNAs. As for the underlying mechanism, the p-Akt/total Akt ratio, nuclear factor erythroid 2-related factor 2 (Nrf2) levels, and heme oxygenase-1 (HO-1) levels were higher in diabetic HUVECs treated with tFNAs. In vivo experiments showed that tFNAs facilitated diabetic wound healing by accelerating vascularization, epithelialization, collagen deposition, and collagen alignment. In conclusion, tFNAs could protect endothelial cell function, reduce inflammation, and impede oxidative damage through their antioxidant activity via the Akt/Nrf2/HO-1 signaling pathway. The application of tFNAs may pave the way for better healing of diabetic wounds.

中文翻译：

通过激活Akt / Nrf2 / HO-1途径，四面体骨架核酸在糖尿病伤口愈合中的抗氧化和促血管生成作用。

当前可用的策略显示在预防慢性糖尿病伤口的发病率和残疾方面效果有限。理想的血管形成对于更好地恢复和预后糖尿病伤口是必不可少的。这项研究旨在调查四面体框架核酸（tFNAs）在糖尿病伤口愈合过程中的血管生成过程中的作用及其潜在机制。体外结果显示，tFNAs处理增强了被晚期糖基化终产物（AGEs）抑制的血管样结构的形成。在细胞活力，迁移能力，一氧化氮（NO）水平和血管内皮生长因子-A（VEGF-A）表达方面检测到正变化。此外，tFNA减弱了糖尿病人脐静脉内皮细胞（HUVEC）中高活性氧（ROS）水平和与氧化损伤和炎症相关的基因表达。至于潜在的机制，在用tFNAs治疗的糖尿病HUVEC中，p-Akt /总Akt比，核因子类红细胞2相关因子2（Nrf2）水平和血红素加氧酶1（HO-1）水平较高。体内实验表明，tFNA通过加速血管生成，上皮形成，胶原蛋白沉积和胶原蛋白排列，促进了糖尿病伤口的愈合。总之，tFNAs可以通过Akt / Nrf2 / HO-1信号通路的抗氧化活性来保护内皮细胞功能，减少炎症并阻止氧化损伤。tFNA的应用可能为更好地治愈糖尿病伤口铺平道路。

更新日期：2020-02-28

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