Tenascin‑C promotes the migration of bone marrow stem cells via toll‑like receptor 4‑mediated signaling pathways: MAPK, AKT and Wnt.
Tenascin‑C promotes the migration of bone marrow stem cells via toll‑like receptor 4‑mediated signaling pathways: MAPK, AKT and Wnt.
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Tenascin-C 通过 Toll 样受体 4 介导的信号通路：MAPK、AKT 和 Wnt 促进骨髓干细胞的迁移
DOI：
10.3892/mmr.2018.8855
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发表时间：
2018-06
影响因子：
3.4
通讯作者：
Huang R
中科院分区：
文献类型：
--
作者：
Ding H;Jin M;Liu D;Wang S;Zhang J;Song X;Huang R
由于移植后细胞的归巢率和增殖率较低，目前干细胞治疗存在局限性。本研究旨在探讨肌腱蛋白-C (TN-C) 对骨髓间充质干细胞 (BMSC) 的影响及其潜在机制。 BMSCs 获自 C57BL/6 小鼠。通过Cell Counting Kit-8法分析BMSCs的存活和增殖，使用Transwell方法评估迁移，并通过免疫细胞化学和免疫荧光评估分化。此外，通过蛋白质印迹法检测蛋白质水平。高浓度的TN-C促进BMSCs的迁移。浓度为 60-90 µmol/ml 的 H2O2 会诱导 BMSC 细胞死亡，因此可用于模拟急性心肌梗死 (AMI) 微环境中的氧化应激。高浓度的TN-C能够保护BMSCs免于细胞死亡，并促进BMSCs的迁移（P<0.05）。然而，TAK-242[Toll样受体4的抑制剂(TLR4)]降低了TN-C的促进作用(P<0.05)。相比之下，TN-C对BMSCs的增殖和分化没有影响。 TN-C降低了p38丝裂原激活蛋白激酶（MAPK）的磷酸化水平，并增加了Ser473蛋白激酶B（AKT）和β-catenin的磷酸化水平，所有这些均被TAK-242抑制（P<0.05）。在模拟的AMI微环境中，TN-C通过TLR4介导的信号通路（包括MAPK、AKT和Wnt）促进BMSCs的迁移。
There are currently limitations in stem cell therapy due to the low rate of homing and proliferation of cells following transplantation. The present study was designed to investigate the effects of Tenascin-C (TN-C) on bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. BMSCs were obtained from C57BL/6 mice. The survival and proliferation of BMSCs was analyzed by Cell Counting Kit-8 assay, migration was evaluated using the Transwell method, and differentiation was assessed by immunocytochemistry and immunofluorescence. In addition, the levels of proteins were detected by western blotting. High concentrations of TN-C promoted the migration of BMSCs. H2O2 at concentrations of 60–90 µmol/ml induced cell death in BMSCs, and thus, it was used to simulate oxidative stress in the microenvironment of acute myocardial infarction (AMI). High concentrations of TN-C were able to protect BMSCs from cell death, and promoted the migration of BMSCs (P<0.05). However, TAK-242 [the inhibitor of Toll-like receptor 4, (TLR4)] reduced the promoting effect of TN-C (P<0.05). By contrast, TN-C had no effect on the proliferation and differentiation of BMSCs. TN-C reduced the phosphorylation levels of p38 mitogen-activated protein kinase (MAPK), and increased the phosphorylation levels of Ser473 protein kinase B (AKT) and β-catenin, all of which were inhibited by TAK-242 (P<0.05). In the simulated AMI microenvironment, TN-C promoted the migration of BMSCs via TLR4-mediated signaling pathways, including MAPK, AKT and Wnt.
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影响因子：
5.4
作者：
Huang, Cuiyuan;Pan, Linghui;Fu, Ruili
通讯作者：
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影响因子：
2.2
作者：
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影响因子：
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5.6
作者：
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影响因子：
4
作者：
Hussey SE;Liang H;Costford SR;Klip A;DeFronzo RA;Sanchez-Avila A;Ely B;Musi N
通讯作者：
Musi N