miRNA-mediated macrophage behaviors responding to matrix stiffness and ox-LDL.

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.

journal_name

J Cell Physiol

authors

Li J,Wang S,Li Y,Zhang N,Gribskov M,Zhang X,Lin M,Shao D,Zhang C,Dai L,Qin C,Duan X,Li J,Xu F,Yang H

doi

10.1002/jcp.29543

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

6139-6153

issue

9

eissn

0021-9541

issn

1097-4652

journal_volume

235

pub_type

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