期刊
AUTOPHAGY
卷 17, 期 10, 页码 2991-3010出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2020.1850608
关键词
3D culture; heme oxygenase 1; hypoxia inducible factor 1 subunit alpha; MSC survival; transplantation
类别
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT, and Future Planning [2015R1A5A2009124, 2020R1C1C1004733]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2018R1D1A1B0704970, 2020R1A6A1A03044512]
- National Research Foundation of Korea [2020R1C1C1004733] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The study found that 3D-cultured MSCs (MSC3D) showed highly induced autophagy and suppressed ROS production compared to 2D-cultured MSCs (MSC2D). Autophagy induction significantly influenced the cell viability and apoptotic activity in MSC3D. The HIF1A-HMOX1 axis played a crucial role in modulating ROS production and autophagy induction in MSC3D.
Mesenchymal stromal cells (MSCs) have received attention as promising therapeutic agents for the treatment of various diseases. However, poor post-transplantation viability is a major hurdle in MSC-based therapy, despite encouraging results in many inflammatory disorders. Recently, three dimensional (3D)-cultured MSCs (MSC3D) were shown to have higher cell survival and enhanced anti-inflammatory effects, although the underlying mechanisms have not yet been elucidated. In this study, we investigated the molecular mechanisms by which MSC3D gain the potential for enhanced cell viability. Herein, we found that macroautophagy/autophagy was highly induced and ROS production was suppressed in MSC3D as compared to 2D-cultured MSCs (MSC2D). Interestingly, inhibition of autophagy induction caused decreased cell viability and increased apoptotic activity in MSC3D. Furthermore, modulation of ROS production was closely related to the survival and apoptosis of MSC3D. We also observed that HMOX1 (heme oxygenase 1) was significantly up-regulated in MSC3D. In addition, gene silencing of HMOX1 caused upregulation of ROS production and suppression of the genes related to autophagy. Moreover, inhibition of HIF1A (hypoxia inducible factor 1 subunit alpha) caused suppression of HMOX1 expression in MSC3D, indicating that the HIF1A-HMOX1 axis plays a crucial role in the modulation of ROS production and autophagy induction in MSC3D. Finally, the critical role of autophagy induction on improved therapeutic effects of MSC3D was further verified in dextran sulfate sodium (DSS)-induced murine colitis. Taken together, these results indicated that autophagy activation and modulation of ROS production mediated via the HIF1A-HMOX1 axis play pivotal roles in enhancing the viability of MSC3D.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据