Tenascin‑C promotes the migration of bone marrow stem cells via toll‑like receptor 4‑mediated signaling pathways: MAPK, AKT and Wnt

Ding,Huaiyu; Jin,Mingyu; Liu,Dai; Wang,Shujing; Zhang,Jianing; Song,Xiantao; Huang,Rongchong

doi:10.3892/mmr.2018.8855

Tenascin‑C promotes the migration of bone marrow stem cells via toll‑like receptor 4‑mediated signaling pathways: MAPK, AKT and Wnt

Authors:
- Huaiyu Ding
- Mingyu Jin
- Dai Liu
- Shujing Wang
- Jianing Zhang
- Xiantao Song
- Rongchong Huang
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, College of Life Sciences and Pharmacy, Dalian University of Technology, Dalian, Liaoning 116027, P.R. China, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing 100029, P.R. China
Published online on: April 5, 2018 https://doi.org/10.3892/mmr.2018.8855
Pages: 7603-7610
Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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