Inhibition of miR-29b suppresses MAPK signaling pathway through targeting SPRY1 in atherosclerosis

• Published in: Vascular pharmacology Vol. 102; pp. 29 - 36
• Main Authors: Lu, Zhen, Wang, Feng, Yu, Pei, Wang, Xue, Wang, Yuan, Tang, Song-tao, Zhu, Hua-qing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2018; Elsevier Science Ltd
• Subjects: 3' Untranslated Regions; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Antagomirs - genetics; Antagomirs - metabolism; Aorta; Apolipoprotein E; Arteriosclerosis; Atherosclerosis; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Binding Sites; Cardiovascular disease; Cardiovascular diseases; Cells, Cultured; Disease Models, Animal; Down-Regulation; Endothelial cells; Endothelium; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Gene expression; Heart diseases; Homology; Human Umbilical Vein Endothelial Cells - metabolism; Human Umbilical Vein Endothelial Cells - pathology; Humans; Inhibition; Inhibitor drugs; MAP kinase; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice, Knockout, ApoE; MicroRNAs - genetics; MicroRNAs - metabolism; Mitogen-Activated Protein Kinases - metabolism; mRNA; NAD(P)H oxidase; NADPH Oxidases - metabolism; Oxidase; Pathogenesis; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phosphorylation; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction; Signaling; Tissues; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Umbilical vein
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2018.01.006

The treatment of atherosclerosis (AS), a severe condition associated with the pathogenesis of cardiovascular diseases (CVDs), is still not satisfactory worldwide. In this study, we aim to investigate whether protein sprout homologue 1 (SPRY1), a upstream mediator of MAPK signal pathway, is the target of miR-29b in vascular endothelium during the development of AS. ApoE−/− mice model was established, and an inverse correlation was noticed between level of miR-29b and SPRY1 expression in the aortic tissues. Meanwhile, the tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) expression and NADPH oxidase activity were up-regulated in atherosclerotic tissues. In vitro experiments were carried out to investigate the roles of miR-29b in regulating the expression of SPRY1 in cultured human umbilical vein endothelial cells (HUVECs). We found that miR-29b mimic and antagomir could modulate the expression of SPRY1 protein in cultured HUVECs. However, the expression of SPRY1 mRNA showed no statistical difference when treating with miR-29b mimic or antagomir. These indicated that the modulation of SPRY1 induced by miR-29b was at the posttranslational level. Dural luciferase reporter assay was conducted to detect the potential interaction between miR-29b and the 3'UTR of SPRY1, which indicated that SPRY1 was a target of miR-29b. Besides, miR-29b antagomir induced decrease of TNF-α, ROS production and NADPH oxidase activity and down-regulated the expression of p-ERK and p-p38 in the presence of oxLDL. In conclusion, inhibition of miR-29b could attenuate AS by inhibiting the SPRY1/MAPK signaling pathway and inflammation in aorta. In future, treatment options based on miR-29b may be applicable for the treatment of AS. [Display omitted]