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miRNA-mediated macrophage behaviors responding to matrix stiffness and ox-LDL |
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| Authors: | Jing Li Sufang Wang Yuhui Li Nu Zhang Michael Gribskov Xi Zhang Min Lin Dongyan Shao Chen Zhang Liangliang Dai Chuanguang Qin Xianglong Duan Juntang Li Feng Xu Hui Yang |
| Affiliation: | 1. School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China Center of Special Environmental Biomechanics & Biomedical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China Key Laboratory on Space Physics and Chemistry of Ministry of Education and Key Laboratory on Macromolecular Science & Technology of Shanxi Province, Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China;2. School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China Center of Special Environmental Biomechanics & Biomedical Engineering, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China;3. Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, P.R. China The Key Library of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, P.R. China;4. Department of Biological Sciences, Purdue University, West Lafayette, Indiana Department of Computer Science, Purdue University, West Lafayette, Indiana;5. School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China;6. Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China;7. Key Laboratory on Space Physics and Chemistry of Ministry of Education and Key Laboratory on Macromolecular Science & Technology of Shanxi Province, Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China;8. Second Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, P.R. China Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, P.R. China;9. Collaborative Innovation Centre of Medical Engineering, Luoyang, Henan, China;10. Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, P.R. China |
| Abstract: | Atherosclerosis is one of the leading causes of morbidity and mortality, mainly due to the immune response triggered by the recruitment of monocytes/macrophages in the artery wall. Accumulating evidence have shown that matrix stiffness and oxidized low-density lipoproteins (ox-LDL) play important roles in atherosclerosis through modulating cellular behaviors. However, whether there is a synergistic effect for ox-LDL and matrix stiffness on macrophages behavior has not been explored yet. In this study, we developed a model system to investigate the synergistic role of ox-LDL and matrix stiffness on macrophage behaviors, such as migration, inflammatory and apoptosis. We found that there was a matrix stiffness-dependent behavior of monocyte-derived macrophages stimulated with ox-LDL. What's more, macrophages were more sensitive to ox-LDL on the stiff matrices compared to cells cultured on the soft matrices. Through next-generation sequencing, we identified miRNAs in response to matrix stiffness and ox-LDL and predicted pathways that showed the capability of miRNAs in directing macrophages fates. Our study provides a novel understanding of the important synergistic role of ox-LDL and matrix stiffness in modulating macrophages behaviors, especially through miRNAs signaling pathways, which could be potential key regulators in atherosclerosis and immune-targeted therapies. |
| Keywords: | atherosclerosis macrophage matrix stiffness miRNA ox-LDL |