血小板衍生生长因子 BB 通过 PI3K、P38MAPK 和 NF-κB 通路促进血管细胞黏附分子-1 的表达，介导脑胶质瘤诱导骨髓间充质干细胞的迁移。
Platelet-derived growth factor BB mediates the glioma-induced migration of bone marrow-derived mesenchymal stem cells by promoting the expression of vascular cell adhesion molecule-1 through the PI3K, P38 MAPK and NF-κB pathways.
机构信息
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
出版信息
Oncol Rep. 2013 Dec;30(6):2755-64. doi: 10.3892/or.2013.2780. Epub 2013 Oct 2.
Platelet-derived growth factor BB (PDGFBB) has been shown to activate the migration of bone marrow-derived mesenchymal stem cells (BM-MSCs), and to contribute to mediating the tropism of BM-MSCs towards gliomas. However, the exact mechanism of this migratory behavior remains to be elucidated. The present study investigated the role of vascular cell adhesion molecule-1 (VCAM-1) in the PDGFBB-induced migration of BM-MSCs, the effect of PDGFBB on VCAM-1 expression of BM-MSCs and related signaling pathways involved in this process. Rat BM-MSCs were isolated and cultured by their characteristics of adherence to plastics. The concentrations of PDGFBB in the conditioned medium of C6 and U87 cells were measured using the ELISA method. In vitro migration assays using a VCAM-1 blocking antibody were performed to evaluate the role of VCAM-1 in PDGFBB-induced migration of BM-MSCs. The effect of rat recombinant PDGFBB on VCAM-1 expression of BM-MSCs was studied by RT-PCR and western blotting. LY294002, SB203580, PD98059, SP600125 and BAY11-7082 were used to explore the role of PI3K, p38 MAPK, MEK, JNK and NF-κB in the related intracellular signal transduction of PDGFBB stimulation on VCAM-1 expression of BM-MSCs. The data demonstrated that the neutralization of VCAM-1 inhibited the migration of BM-MSCs induced by PDGFBB. Additionally, PDGFBB stimulation increased VCAM-1 expression of BM-MSCs, which could be inhibited by LY294002, SB203580 and BAY11-7082. It is reasonable to conclude that PDGFBB significantly enhanced the expression of VCAM-1 in BM-MSCs, which facilitated the migration of BM-MSCs towards PDGFBB. PI3K, p38 MAPK and NF-κB were involved in the signal transduction of this process.
血小板衍生生长因子 BB（PDGFBB）已被证明能激活骨髓间充质干细胞（BM-MSCs）的迁移，并有助于介导 BM-MSCs 向神经胶质瘤的趋化性。然而，这种迁移行为的确切机制仍有待阐明。本研究探讨了血管细胞黏附分子-1（VCAM-1）在 PDGFBB 诱导的 BM-MSCs 迁移中的作用、PDGFBB 对 BM-MSCs 中 VCAM-1 表达的影响以及该过程中涉及的相关信号通路。通过其对塑料的黏附特性分离和培养大鼠 BM-MSCs。采用 ELISA 法测定 C6 和 U87 细胞条件培养基中 PDGFBB 的浓度。通过 VCAM-1 阻断抗体的体外迁移实验，评估 VCAM-1 在 PDGFBB 诱导的 BM-MSCs 迁移中的作用。通过 RT-PCR 和 Western blot 研究大鼠重组 PDGFBB 对 BM-MSCs 中 VCAM-1 表达的影响。采用 LY294002、SB203580、PD98059、SP600125 和 BAY11-7082 探讨 PI3K、p38MAPK、MEK、JNK 和 NF-κB 在 PDGFBB 刺激相关细胞内信号转导对 BM-MSCs 中 VCAM-1 表达的作用。结果表明，中和 VCAM-1 抑制了 PDGFBB 诱导的 BM-MSCs 迁移。此外，PDGFBB 刺激增加了 BM-MSCs 中 VCAM-1 的表达，该作用可被 LY294002、SB203580 和 BAY11-7082 抑制。由此可以合理地得出结论，PDGFBB 显著增强了 BM-MSCs 中 VCAM-1 的表达，从而促进了 BM-MSCs 向 PDGFBB 的迁移。PI3K、p38MAPK 和 NF-κB 参与了这一过程的信号转导。
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