Lu Xiaodan, Lin Yifan, Lin Xiuying, Zhang Qiang, Wang Zihang, Mi Xuguang, Wang Ruobing, Zhang Xiaofang, Luan Xu, Liu Yan, Li Bing, Tan Yan, Fang Yanqiu
Diagnostic Medical Center, Jilin Province People's Hospital, Changchun 130021, China.
School of Medicine, Changchun University of Chinese Medicine, Changchun 130021, China.
Biophys Rep. 2021 Apr 30;7(2):142-151. doi: 10.52601/bpr.2021.200046.
Human umbilical cord mesenchymal stem cells (HUC-MSCs) are pluripotent and functional in many biological processes, by which releasing secretary factors to promote the self-repairing of damaged tissue or developing into functional cell at local organ. However, there is a high risk that oxidative stress would reduce the pluripotency and factor-secretion during the preparation and transplantation. Therefore, reducing oxidative stress is expected to improve the efficacy of HUC-MSCs therapy. Zinc (Zn) is an essential trace element which involves in the resistance of oxidative stress. To investigate Zn-regulated signaling pathways, we have profiled the gene expression at transcriptome level in primary HUC-MSCs treated with zinc sulfate, followed with GO and KEGG gene enrichment analysis. Zn treatment improved signal pathways for mineral absorption, cell growth, and cell death. Zn deficiency was mimicked by TPEN administration, which suppressed cell proliferation and reduced the expression of HUC-MSCs surface stem cell markers CD73, CD90 and CD105 by flow cytometry. Nuclear factor erythrocyte 2 related factor 2 (Nrf2) plays an important role in antioxidant biological processes. treatment of Zn significantly increased Nrf2 and Sirt3 expression at gene level and protein level respectively. Zn supplementation inhibited TPEN-induced failure of cell survival and reversed the reduction of Nrf2 and Sirt3 expression, which further reduced the production of ROS. Zn successfully presented its anti-oxidation effect by activating Nrf2/Sirt3 signaling pathway in HUC-MSCs. Zn supplementation may improve the efficacy of HUC-MSCs therapy with reduced oxidative stress.
人脐带间充质干细胞（HUC-MSCs）具有多能性，在许多生物学过程中发挥作用，通过释放分泌因子促进受损组织的自我修复或在局部器官发育为功能细胞。然而，在制备和移植过程中，氧化应激有很高的风险会降低其多能性和因子分泌。因此，降低氧化应激有望提高HUC-MSCs治疗的疗效。锌（Zn）是一种必需的微量元素，参与氧化应激的抵抗。为了研究锌调节的信号通路，我们对硫酸锌处理的原代HUC-MSCs进行了转录组水平的基因表达谱分析，随后进行了GO和KEGG基因富集分析。锌处理改善了矿物质吸收、细胞生长和细胞死亡的信号通路。通过施用TPEN模拟锌缺乏，这抑制了细胞增殖，并通过流式细胞术降低了HUC-MSCs表面干细胞标志物CD73、CD90和CD105的表达。核因子红细胞2相关因子2（Nrf2）在抗氧化生物学过程中起重要作用。锌处理分别在基因水平和蛋白质水平显著增加了Nrf2和Sirt3的表达。补充锌抑制了TPEN诱导的细胞存活失败，并逆转了Nrf2和Sirt3表达的降低，这进一步减少了活性氧的产生。锌通过激活HUC-MSCs中的Nrf2/Sirt3信号通路成功发挥了其抗氧化作用。补充锌可能通过降低氧化应激提高HUC-MSCs治疗的疗效。
