MicroRNA-155 promotes atherosclerosis-signaling pathway through targeting gene/SOCS1 and IRAKM

Abstract

MiR-155 plays a role in the regulates various aspects of innate and adaptive immune response, physiological and pathological processes. Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and attenuate the progression of cardiovascular diseases. Up-regulation of proinflammatory cytokines plays a central role in atherosclerosis. In this study, we investigated the role of miR-155 in regulating proinflammatory response in atherosclerosis. Hyperlipidemic C57BL/6 male mice model were fed with atherogenic-diet for 12-weeks. MiR-155 positively regulates proinflammatory cytokines and we found increased TNFα, IL-1b, IL-6 mRNA and NF-kB in hyperlipidemic mice. Furthermore, increased miR-155 levels are correlated with proinflammatory cytokine expression in hyperlipidemic mice. To understand the mechanism by which miR-155 regulates proinflammatory cytokines in atherosclerosis, we evaluated the miR-155 target genes SOCS1 and IRAKM. We found increased miR-155 and decreased expression of SOCS1 and IRAKM in hyperlipidemic mice. Interestingly inhibition of miR-155 by using a specific miR-155 silencing, inhibited proinflammatory cytokine in hyperlipidemic mice, suggesting a role of miR-155 in immune response regulation. Based on these observations, we conclude that miR-155 modulates proinflammatory response in hyperlipidemic mice via regulation of SOCS1 and IRAKM expression. Thus, modulation of miR-155 could be a strategy to regulate atherogenic diet-induced atherosclerosis where proinflammatory cytokine plays significant role in disease progression.