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MiR‐135a represses oxidative stress and vascular inflammatory events via targeting toll‐like receptor 4 in atherogenesis
Author(s) -
Du XianJin,
Lu JingMin
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26819
Subject(s) - oxidative stress , inflammation , cd36 , apoptosis , tlr4 , microbiology and biotechnology , receptor , microrna , cancer research , toll like receptor , chemistry , immunology , biology , innate immune system , gene , biochemistry
Plenty of microRNAs have been identified as critical mediators in atherosclerosis progression, which is still a great threat to human health. Oxidative stress and inflammation have been implicated to contribute a lot to atherosclerosis development. MiR‐135a is abnormally expressed in various cancer types, however its function in atherosclerosis is largely unexplored. Ox‐LDL is commonly recognized as a crucial atherosclerosis regulator. In our current study, we observed ox‐LDL was able to induce RAW264.7 cell apoptosis and meanwhile miR‐135a was restrained by ox‐LDL both dose‐dependently and time‐ dependently. CD36 has been reported to participate in atherosclerosis process and miR‐135a mimics can inhibit its expression while miR‐135a inhibitors exhibited a reverse phenomenon. Meanwhile, miR‐135a overexpression can suppress foam cell formation, TC, TG levels, and cell apoptosis induced by 20 µg/mL ox‐LDL. Subsequently, it was found that miR‐135a overexpression can inhibit oxidative stress by decreasing ROS, MDA levels, and increasing SOD levels. Reversely, miR‐135a inhibition demonstrated an inhibitory effect in vitro. Apart from these, miR‐135a can also modulate inflammation molecules including IL‐6, IL‐1β, and TNF‐α. TLR4 was predicted as a target of miR‐135a and the negative correlation between them was confirmed by dual‐luciferase reporter assay in our study. This work improves our understanding of atherosclerosis events mediated by miR‐135a/TLR4 and helps to develop new approaches for atherosclerosis.