Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
Cells. 2022 Aug 18;11(16):2568. doi: 10.3390/cells11162568.
Chronic wounds resulting from diabetes are a major health concern in both industrialized and developing countries, representing one of the leading causes of disability and death. This study aimed to investigate the effect of adipose mesenchymal stem cell-derived exosomes (ADSC-exos) on diabetic wounds and the mechanism underlying this effect. The results showed that ADSC-exos could improve oxidative stress and secretion of inflammatory cytokines in diabetic wounds, thereby increasing periwound vascularization and accelerating wound healing. At the cellular level, ADSC-exos reduced reactive oxygen species (ROS) generation in human umbilical vein endothelial cells (HUVECs) and improved mitochondrial function in a high-glucose environment. Moreover, the Western blot analysis showed that the high-glucose environment decreased Sirtuin 3 (SIRT3) expression, while exosome treatment increased SIRT3 expression. The activity of superoxide dismutase 2 (SOD2) was enhanced, and the level of inflammatory cytokines was decreased. Further, SIRT3 interference experiments indicated that the effects of ADSC-exos on oxidative stress and angiogenesis were partly dependent on SIRT3. After SIRT3 was inhibited, ROS production increased, while mitochondrial membrane potential and SOD2 activity decreased. These findings confirmed that ADSC-exos could improve the level of high-glucose-induced oxidative stress, promote angiogenesis, and reduce mitochondrial functional impairment and the inflammatory response by regulating SIRT3/SOD2, thus promoting diabetic wound healing.
糖尿病引起的慢性伤口是工业化国家和发展中国家的主要健康问题，也是导致残疾和死亡的主要原因之一。本研究旨在探讨脂肪间充质干细胞衍生的外泌体（ADSC-exos）对糖尿病伤口的影响及其作用机制。结果表明，ADSC-exos 可改善糖尿病伤口的氧化应激和炎症细胞因子的分泌，从而增加伤口周围血管生成并加速伤口愈合。在细胞水平上，ADSC-exos 可减少人脐静脉内皮细胞（HUVEC）中活性氧（ROS）的产生，并改善高糖环境中的线粒体功能。此外，Western blot 分析表明，高糖环境降低了 Sirtuin 3（SIRT3）的表达，而外泌体处理则增加了 SIRT3 的表达。超氧化物歧化酶 2（SOD2）的活性增强，炎症细胞因子的水平降低。进一步的 SIRT3 干扰实验表明，ADSC-exos 对氧化应激和血管生成的作用部分依赖于 SIRT3。抑制 SIRT3 后，ROS 产生增加，而线粒体膜电位和 SOD2 活性降低。这些发现证实，ADSC-exos 通过调节 SIRT3/SOD2 可改善高糖诱导的氧化应激水平，促进血管生成，并减少线粒体功能障碍和炎症反应，从而促进糖尿病伤口愈合。
