Department of Gastroenterology, Ningbo First Hospital, 59 Liuting Street, Ningbo, 315010, China.
Ningbo University School of Medicine, No 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.
Dig Dis Sci. 2019 Jan;64(1):113-122. doi: 10.1007/s10620-018-5290-2. Epub 2018 Sep 27.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Recent studies have reported that circular RNAs (circRNAs) are important regulators of hepatic steatosis. However, the role and mechanism of circRNA in NAFLD are poorly understood.
This study is to reveal the role and mechanism of circRNA in NAFLD.
Through NAFLD-related circRNA microarrays, we used real-time quantitative reverse transcription-polymerase chain reaction to screen circScd1 levels in control and test groups of mice fed a high-fat diet. RNA interference and over-expression plasmid vectors were used to manipulate the expression of circScd1, and the biological effects were evaluated by oil red staining, triglyceride detection, and western blot analysis.
CircScd1 expression was significantly lower in NAFLD tissues than in control tissues. Moreover, over-expression of circScd1 significantly inhibited the formation of lipid droplets. Western blot analyses showed that the protein levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were significantly increased. However, knockdown of circScd1 significantly promoted the degree of hepatocellular lipidosis and reduced the expression levels of JAK2 and STAT5.
Aberrant expression of circScd1 affects the extent of hepatocellular lipidosis in NAFLD and promotes fatty liver disease via the JAK2/STAT5 pathway.
非酒精性脂肪性肝病（NAFLD）是富裕国家最常见的肝脏疾病之一。最近的研究报告称，环状 RNA（circRNA）是肝脂肪变性的重要调节因子。然而，circRNA 在 NAFLD 中的作用和机制仍知之甚少。
本研究旨在揭示 circRNA 在 NAFLD 中的作用和机制。
通过与 NAFLD 相关的 circRNA 微阵列，我们使用实时定量逆转录聚合酶链反应筛选高脂饮食喂养的对照组和实验组小鼠中 circScd1 的水平。采用 RNA 干扰和过表达质粒载体来操纵 circScd1 的表达，并通过油红染色、甘油三酯检测和 Western blot 分析来评估其生物学效应。
与对照组相比，NAFLD 组织中 circScd1 的表达显著降低。此外，circScd1 的过表达显著抑制了脂滴的形成。Western blot 分析表明，Janus 激酶 2（JAK2）和信号转导子和转录激活子 5（STAT5）的蛋白水平显著增加。然而，circScd1 的敲低显著促进了肝细胞脂肪变性的程度，并降低了 JAK2 和 STAT5 的表达水平。
circScd1 的异常表达影响 NAFLD 中肝细胞脂肪变性的程度，并通过 JAK2/STAT5 通路促进脂肪肝疾病。
