General Hospital of Southern Theater Command of PLA, The First School of Clinical Medicine, Southern Medical University, Guangzhou 510010, China.
General Hospital of Southern Theater Command of PLA, Guangzhou University of Chinese Medicine, Guangzhou 510010, China.
Oxid Med Cell Longev. 2023 Feb 20;2023:2345279. doi: 10.1155/2023/2345279. eCollection 2023.
As a critical member in wound healing, vascular endothelial cells (ECs) impaired under high levels of reactive oxygen species (ROS) would hamper neovascularization. Mitochondria transfer can reduce intracellular ROS damage under pathological condition. Meanwhile, platelets can release mitochondria and alleviate oxidative stress. However, the mechanism by which platelets promote cell survival and reduce oxidative stress damage has not been clarified. Here, first, we selected ultrasound as the best method for subsequent experiments by detecting the growth factors and mitochondria released from manipulation platelet concentrates (PCs), as well as the effect of manipulation PCs on the proliferation and migration of HUVECs. Then, we found that sonicate platelet concentrates (SPC) decreased the level of ROS in HUVECs treated with hydrogen peroxide in advance, increased mitochondrial membrane potential, and reduced apoptosis. By transmission electron microscope, we saw that two kinds of mitochondria, free or wrapped in vesicles, were released by activated platelets. In addition, we explored that platelet-derived mitochondria were transferred to HUVECs partly by means of dynamin-dependent clathrin-mediated endocytosis. Consistently, we determined that platelet-derived mitochondria reduced apoptosis of HUVECs caused by oxidative stress. What is more, we screened survivin as the target of platelet-derived mitochondria via high-throughput sequencing. Finally, we demonstrated that platelet-derived mitochondria promoted wound healing in vivo. Overall, these findings revealed that platelets are important donors of mitochondria, and platelet-derived mitochondria can promote wound healing by reducing apoptosis caused by oxidative stress in vascular endothelial cells. And survivin is a potential target. These results further expand the knowledge of the platelet function and provide new insights into the role of platelet-derived mitochondria in wound healing.
作为伤口愈合的关键成员，在高水平活性氧（ROS）下受损的血管内皮细胞（ECs）会阻碍新血管的形成。线粒体转移可以在病理条件下减少细胞内 ROS 损伤。同时，血小板可以释放线粒体并减轻氧化应激。然而，血小板促进细胞存活和减少氧化应激损伤的机制尚未阐明。在这里，我们首先通过检测操作血小板浓缩物（PCs）释放的生长因子和线粒体，以及操作 PCs 对 HUVECs 增殖和迁移的影响，选择超声作为后续实验的最佳方法。然后，我们发现超声处理的血小板浓缩物（SPC）降低了预先用过氧化氢处理的 HUVECs 中的 ROS 水平，增加了线粒体膜电位，减少了细胞凋亡。通过透射电子显微镜，我们看到了两种线粒体，即自由或包裹在囊泡中的线粒体，是由激活的血小板释放的。此外，我们探讨了血小板衍生的线粒体部分通过依赖 dynamin 的网格蛋白介导的内吞作用被转移到 HUVECs 中。一致地，我们确定血小板衍生的线粒体减少了氧化应激引起的 HUVECs 的凋亡。更重要的是，我们通过高通量测序筛选出了血小板衍生的线粒体的靶标 survivin。最后，我们证明了血小板衍生的线粒体促进了体内伤口愈合。总的来说，这些发现揭示了血小板是线粒体的重要供体，血小板衍生的线粒体可以通过减少血管内皮细胞氧化应激引起的细胞凋亡来促进伤口愈合。而且 survivin 是一个潜在的靶点。这些结果进一步扩展了血小板功能的知识，并为血小板衍生的线粒体在伤口愈合中的作用提供了新的见解。
