TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts.
TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts.
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TNF-α通过NF-κB途径促进MSC在氧化应激下的存活和迁移，以减轻静脉移植物中内膜增生的衰减。
DOI：
10.1111/jcmm.13131
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发表时间：
2017-09
影响因子：
5.3
通讯作者：
Song G
中科院分区：
文献类型：
--
作者：
Bai X;Xi J;Bi Y;Zhao X;Bing W;Meng X;Liu Y;Zhu Z;Song G
血管内皮损伤引起的氧化应激参与了血管内膜增生（IH）。间充质干细胞（MSCs）能够返回损伤的内膜并促进内皮细胞的修复。然而，在氧化应激下，细胞间充质干细胞凋亡增加，同时功能活性降低。因此，我们研究肿瘤坏死因子α (tumor necrosis factor - α, TNF - α)是否能促进MSCs在氧化应激下的存活和活性，从而更有效地降低IH，并确定NF - κB通路在其中的作用。在这项研究中，我们用TNF - α (TNF - α - PCMSCs)预处理MSCs 24小时，并测量IKK/NF - κB通路的激活情况。EdU和transwell实验评估TNF - α - PCMSCs的增殖和迁移。通过分析Bcl - 2和CXCR4蛋白的表达，评估氧化应激条件下TNF - α - PCMSCs的凋亡和迁移。将TNF - α - PCMSCs移植到静脉移植模型中，跟踪细胞归巢，并测量血管内皮细胞凋亡和IH。结果表明，TNF‐α促进MSCs的增殖和迁移。此外，氧化应激下TNF - α - PCMSCs的存活和迁移能力均得到增强。经TNF‐α预处理后，大量MSCs向移植物内膜迁移，新生内膜的形成明显减少。这些作用可被ikkxii （NF‐κB抑制剂）部分消除。上述结果表明，TNF - α预处理可通过NF - κB途径促进MSCs在氧化应激下的存活和迁移，从而减轻移植物IH。
The oxidative stress caused by endothelial injury is involved in intimal hyperplasia (IH) in vein grafts. Mesenchymal stem cells (MSCs) can home to injured intima and promote endothelial repair. However, MSC apoptosis is increased accompanied by decreased functional activity under oxidative stress. Thus, we investigate whether tumour necrosis factor‐α (TNF‐α) can promote the survival and activity of MSCs under oxidative stress to reduce IH more effectively, and establish what role the NF‐κB pathway plays in this. In this study, we preconditioned MSCs with TNF‐α (TNF ‐α‐PCMSCs) for 24 hrs and measured the activation of the IKK/NF‐κB pathway. EdU and transwell assays were performed to assess proliferation and migration of TNF ‐α‐PCMSCs. Apoptosis and migration of TNF ‐α‐ PCMSCs were evaluated in conditions of oxidative stress by analysis of the expression of Bcl‐2 and CXCR4 proteins. TNF ‐α‐ PCMSCs were transplanted into a vein graft model, so that cell homing could be tracked, and endothelial apoptosis and IH of vein grafts were measured. The results demonstrated that TNF‐α promotes proliferation and migration of MSCs. Furthermore, survival and migration of TNF ‐α‐ PCMSCs under oxidative stress were both enhanced. A greater number of MSCs migrated to the intima of vein grafts after preconditioning with TNF‐α, and the formation of neointima was significantly reduced. These effects could be partially abolished by IKK XII (NF‐κB inhibitor). All these results indicate that preconditioning with TNF‐α can promote survival and migration of MSCs under oxidative stress via the NF‐κB pathway and thus attenuate IH of vein grafts.
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影响因子：
3.6
作者：
Gu Y;Zhang Y;Bi Y;Liu J;Tan B;Gong M;Li T;Chen J
通讯作者：
Chen J
影响因子：
5.3
作者：
Imamura, Hirotoshi;Ohta, Tsuyoshi;Kikuta, Ken-ichiro
通讯作者：
Kikuta, Ken-ichiro
影响因子：
4.8
作者：
Helbig, G;Christopherson, KW;Nakshatri, H
通讯作者：
Nakshatri, H
影响因子：
2.4
作者：
Liu L;Liu L;Shi J;Tan M;Xiong J;Li X;Hu Q;Yi Z;Mao D
通讯作者：
Mao D
DOI：
10.1111/hepr.12411
发表时间：
2015-07
期刊：
Hepatology research : the official journal of the Japan Society of Hepatology
影响因子：
--
作者：
Saiman Y;Jiao J;Fiel MI;Friedman SL;Aloman C;Bansal MB
通讯作者：
Bansal MB