Chen Chao-Feng, Huang Jinyu, Li Hong, Zhang Chu, Huang Xurui, Tong Guoxin, Xu Yi-Zhou
Department of Cardiology, Hangzhou First People's Hospital, Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, China.
Department of Cardiology, Hangzhou First People's Hospital, Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, China.
Gene. 2015 Jul 10;565(2):246-51. doi: 10.1016/j.gene.2015.04.014. Epub 2015 Apr 9.
Adiponectin exerts anti-atherosclerosis property through its 2 receptors (AdipoR1 and AdipoR2). The mechanism regulating the expression of adiponectin receptors is unclear. Bioinformatics analysis showed that miR-221 targeted the 3'-untranslated region (3'UTR) of the AdipoR1 mRNA. The protein level and the mRNA level of AdipoR1 were reduced when miR-221 was expressed in human umbilical vein endothelial cells (HUVECs). Meanwhile, miR-221 repressed the activity of luciferase reporter containing the 3'UTR of AdipoR1. The inhibitory effect of miR-221 was abolished when the miR-221 binding site within the AdipoR1 3'UTR was deleted. Overexpression of miR-221 inhibited adiponectin-stimulated nitric oxide (NO) production in HUVECs. Furthermore, miR-221 abolished the inhibitory effect of adiponectin on NF-kB activation and the expression of adhesion molecules. Altogether, these results indicated that miR-221 targets AdipoR1 to regulate endothelial inflammatory response.
脂联素通过其2种受体（脂联素受体1和脂联素受体2）发挥抗动脉粥样硬化特性。调节脂联素受体表达的机制尚不清楚。生物信息学分析表明，miR-221靶向脂联素受体1信使核糖核酸（mRNA）的3'非翻译区（3'UTR）。当在人脐静脉内皮细胞（HUVECs）中表达miR-221时，脂联素受体1的蛋白质水平和mRNA水平降低。同时，miR-221抑制含有脂联素受体1 3'UTR的荧光素酶报告基因的活性。当脂联素受体1 3'UTR内的miR-221结合位点缺失时，miR-221的抑制作用被消除。miR-221的过表达抑制了HUVECs中脂联素刺激的一氧化氮（NO）生成。此外，miR-221消除了脂联素对核因子-κB（NF-κB）激活和黏附分子表达的抑制作用。总之，这些结果表明，miR-221靶向脂联素受体1以调节内皮炎症反应。
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