Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Oxid Med Cell Longev. 2018 Jan 21;2018:1023025. doi: 10.1155/2018/1023025. eCollection 2018.
The poor survival rate of mesenchymal stromal cells (MSC) transplanted into recipient lungs greatly limits their therapeutic efficacy for diseases like bronchopulmonary dysplasia (BPD). The aim of this study is to evaluate the effect of thioredoxin-1 (Trx-1) overexpression on improving the potential for bone marrow-derived mesenchymal stromal cells (BMSCs) to confer resistance against hyperoxia-induced cell injury.
80% O was used to imitate the microenvironment surrounding-transplanted cells in the hyperoxia-induced lung injury . BMSC proliferation and apoptotic rates and the levels of reactive oxygen species (ROS) were measured. The effects of Trx-1 overexpression on the level of antioxidants and growth factors were investigated. We also investigated the activation of apoptosis-regulating kinase-1 (ASK1) and p38 mitogen-activated protein kinases (MAPK).
Trx-1 overexpression significantly reduced hyperoxia-induced BMSC apoptosis and increased cell proliferation. We demonstrated that Trx-1 overexpression upregulated the levels of superoxide dismutase and glutathione peroxidase as well as downregulated the production of ROS. Furthermore, we illustrated that Trx-1 protected BMSCs against hyperoxic injury via decreasing the ASK1/P38 MAPK activation rate.
These results demonstrate that Trx-1 overexpression improved the ability of BMSCs to counteract hyperoxia-induced injury, thus increasing their potential to treat hyperoxia-induced lung diseases such as BPD.
间质基质细胞（MSC）移植到受体肺部后的存活率低，极大地限制了它们在治疗支气管肺发育不良（BPD）等疾病方面的疗效。本研究旨在评估过表达硫氧还蛋白-1（Trx-1）对提高骨髓间充质基质细胞（BMSCs）对高氧诱导细胞损伤的抗性的影响。
80%O2 用于模拟高氧诱导肺损伤中移植细胞周围的微环境。测量 BMSC 增殖和凋亡率以及活性氧（ROS）水平。研究了 Trx-1 过表达对抗氧化剂和生长因子水平的影响。我们还研究了凋亡调节激酶-1（ASK1）和丝裂原活化蛋白激酶（MAPK）p38 的激活。
过表达 Trx-1 显著降低了高氧诱导的 BMSC 凋亡并增加了细胞增殖。我们表明，过表达 Trx-1 上调了超氧化物歧化酶和谷胱甘肽过氧化物酶的水平，同时降低了 ROS 的产生。此外，我们表明 Trx-1 通过降低 ASK1/P38 MAPK 激活率来保护 BMSCs 免受高氧损伤。
这些结果表明，过表达 Trx-1 提高了 BMSCs 对抗高氧诱导损伤的能力，从而增加了它们治疗高氧诱导肺部疾病（如 BPD）的潜力。
