title: TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts.
abstract: 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 ofTNF-α-PCMSCs. Apoptosis and migration ofTNF-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 ofTNF-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.
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xi
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Bing
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Xiangbin
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Zhonglai
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Guangmin
authors.initials: G
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001807:Blood Vessel Prosthesis; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D006965:Hyperplasia; D051550:I-kappa B Kinase / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D054377:Chemokine CXCL12; D016328:NF-kappa B; D020011:Protective Agents; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D051550:I-kappa B Kinase
keywords: MSCs; NF-κB; TNF-α; intimal hyperplasia; oxidative stress; vein graft