Wang Xin, Ma Yan, Yang Long-Yan, Zhao Dong
Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China.
Front Cell Dev Biol. 2020 Dec 3;8:596329. doi: 10.3389/fcell.2020.596329. eCollection 2020.
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 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.
脂肪酸转运蛋白CD36在慢性肝病和非酒精性脂肪性肝病（NAFLD）的起始和发病机制中起重要作用。本研究旨在探讨微小RNA-20a-5p（miR-20a-5p）在NAFLD发病机制中对CD36的调控作用。从NAFLD患者和健康对照者中获取人血浆样本。给小鼠喂食高脂饮食以诱导NAFLD模型。进行组织学染色以检查小鼠肝组织的形态和脂质沉积。采用实时定量聚合酶链反应、双荧光素酶报告基因检测和蛋白质免疫印迹法检测miR-20a-5p与CD36之间的关系。在NAFLD患者、高脂饮食小鼠以及游离脂肪酸（FFA）处理的HepG2细胞或原代小鼠肝细胞中，miR-20a-5p的表达水平降低，同时肝细胞脂质生成增加。miR-20a-5p通过与CD36的3'-非翻译区（UTR）结合来抑制CD36的表达，从而减少脂质积累。然而，在干扰CD36的情况下，进一步抑制miR-20a-5p不会导致脂质过度积累。在本研究中，我们发现miR-20a-5p通过靶向CD36在NAFLD的脂质代谢紊乱中发挥保护作用，这表明miR-20a-5p作为NAFLD生物标志物和治疗靶点的前景。
