MicroRNA-20a-5p Ameliorates Non-alcoholic Fatty Liver Disease via Inhibiting the Expression of CD36.
MicroRNA-20a-5p Ameliorates Non-alcoholic Fatty Liver Disease via Inhibiting the Expression of CD36.
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MicroRNA-20a-5p 通过抑制 CD36 的表达改善非酒精性脂肪肝。
DOI：
10.3389/fcell.2020.596329
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发表时间：
2020
影响因子：
5.5
通讯作者：
Zhao D
中科院分区：
文献类型：
--
作者：
Wang X;Ma Y;Yang LY;Zhao D
脂肪酸转位酶CD 36（fatty acid translocase CD 36，CD 36）在慢性肝病和非酒精性脂肪性肝病（non-alcoholic fatty liver disease，NAFLD）的发生和发病中起重要作用。本研究旨在探讨microRNA-20 a-5 p（miR-20 a-5 p）对CD 36的调控在NAFLD发病机制中的作用。从NAFLD患者和健康对照获得人血浆样品。用高脂饲料喂养小鼠以诱导体内NAFLD模型。采用组织学染色观察小鼠肝组织形态学和脂质沉积情况。采用实时荧光定量PCR、双荧光素酶法和Western blotting检测miR-20 a-5 p与CD 36的关系。在NAFLD患者、HFD小鼠和游离脂肪酸（FFA）处理的HepG 2细胞或原代小鼠肝细胞中，miR-20 a-5 p的表达水平降低，伴随着肝细胞中脂质产生的增加。miR-20 a-5 p通过与CD 36的3 '非翻译区（UTR）结合抑制CD 36的表达以减少脂质积累。但在干扰CD 36的情况下，进一步抑制miR-20 a-5 p不会导致脂质过度积聚。本研究发现miR-20 a-5 p通过靶向CD 36对NAFLD的脂质代谢紊乱起到保护作用，预示了miR-20 a-5 p作为NAFLD生物标志物和治疗靶点的前景。
Fatty acid translocase CD36 (CD36) plays an important role in the initiation and pathogenesis of chronic liver disease and non-alcoholic fatty liver disease (NAFLD). The purpose of this study is to investigate the regulation of microRNA-20a-5p (miR-20a-5p) on CD36 in the pathogenesis of NAFLD. Human plasma samples were obtained from NAFLD patients and healthy controls. Mice were fed with high-fat diet to induce an in vivo NAFLD model. Histology staining was performed to examine the morphology and lipid deposition of mouse liver tissue. Real-time PCR, dual-luciferase assay, and western blotting were employed to detect the relationship between miR-20a-5p and CD36. The expression level of miR-20a-5p was decreased in NAFLD patients, HFD mice, and free fatty acid (FFA)-treated HepG2 cells or primary mouse hepatocytes, accompanied by increased lipid production in hepatocytes. MiR-20a-5p suppressed the expression of CD36 to reduce lipid accumulation via binding to its 3’-untranslated region (UTR). However, under the condition of interference with CD36, further inhibition of miR-20a-5p would not cause lipid over-accumulation. In this study, we found that miR-20a-5p played a protective role in lipid metabolic disorders of NAFLD by targeting CD36, which indicated the prospect of miR-20a-5p as a biomarker and treatment target for NAFLD.