Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
College of Stomatology, Southern Medical University, Guangzhou 510515, China.
Oxid Med Cell Longev. 2019 Jan 9;2019:6595189. doi: 10.1155/2019/6595189. eCollection 2019.
In order to use stem cells as a resource for tissue regeneration, it is necessary to induce expansion . However, during culture, stem cells often lose functional properties and become senescent. Increasing evidence indicates that hypoxic preconditioning with physiological oxygen concentration can maintain the functional properties of stem cells . The purpose of the current study was to test the hypothesis that hypoxic preconditioning with physiological oxygen concentration can maintain the functional properties of stem cells in culture by reducing oxidative stress. studies were performed in primary human dental pulp cells (hDPCs). Reduced levels of oxidative stress and increased cellular "stemness" in response to physiological hypoxia were dependent upon the expression of reactive oxygen species (ROS). Subsequently, RNA-sequencing analysis revealed the increased expression of phosphoinositide 3-kinase (PI3K)/Akt signaling in culture, a pathway which regulates oxidative stress. Furthermore, we found evidence that PI3K/Akt signaling might affect intracellular ROS production by negatively regulating expression of the downstream protein Forkhead Box Protein O1 (FOXO1) and Caspase 3. Collectively, our data show that the PI3K/Akt pathway is activated in response to hypoxia and inhibits oxidative stress in a ROS-dependent manner. This study identified redox-mediated hypoxic preconditioning regulatory mechanisms that may be significant for tissue regeneration.
为了将干细胞用作组织再生的资源，有必要诱导其扩增。然而，在培养过程中，干细胞常常失去功能特性并衰老。越来越多的证据表明，用生理氧浓度进行低氧预处理可以维持干细胞的功能特性。本研究旨在通过减少氧化应激来检验低氧预处理用生理氧浓度可以维持培养中干细胞功能特性的假说。研究在原代人牙髓细胞（hDPCs）中进行。对生理低氧的反应中，氧化应激的减少和细胞“干性”的增加依赖于活性氧（ROS）的表达。随后，RNA 测序分析显示培养过程中磷酸肌醇 3-激酶（PI3K）/Akt 信号的表达增加，该途径调节氧化应激。此外，我们发现证据表明，PI3K/Akt 信号可能通过负调控下游蛋白 Forkhead Box Protein O1（FOXO1）和 Caspase 3 的表达来影响细胞内 ROS 的产生。总之，我们的数据表明，PI3K/Akt 途径在低氧条件下被激活，并以 ROS 依赖的方式抑制氧化应激。这项研究确定了与氧化还原相关的低氧预处理调节机制，这对于组织再生可能具有重要意义。
