Nantong Institute of Liver Disease, Department of Gastroenterology and Hepatology, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, China.
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Sci Rep. 2020 Feb 21;10(1):3201. doi: 10.1038/s41598-020-60138-8.
Non-alcoholic fatty liver disease (NAFLD) is characterized by increased uptake and accumulation of lipids in hepatocytes. Simple steatosis may progress to non-alcoholic steatohepatitis (NASH) with inflammation, hepatocellular injury and fibrosis. CCN1 is an important matrix protein that regulates cell death and promotes immune cell adhesion and may potentially control this process. The role of CCN1 in NASH remains unclear. We investigated the role of CCN1 in the pathogenesis of steatohepatitis. CCN1 upregulation was found to be closely related with steatosis in patients with NASH, obese mice and a FFA-treated hepatocyte model. Controlling the expression of CCN1 in murine NASH models demonstrated that CCN1 increased the severity of steatosis and inflammation. From the sequence results, we found that fatty acid metabolism genes were primarily involved in the MCD mice overexpressing CCN1 compared to the control. Then, the expression of fatty acid metabolism genes was determined using a custom-designed pathway-focused qPCR-based gene expression array. Expression analysis showed that CCN1 overexpression significantly upregulated the expression of fatty acid metabolism-associated genes. In vitro analysis revealed that CCN1 increased the intracellular TG content, the pro-inflammatory cytokines and the expression level of apoptosis-associated proteins in a steatosis model using murine primary hepatocytes. We identified CCN1 as an important positive regulator in NASH.
非酒精性脂肪性肝病（NAFLD）的特征是肝细胞内脂质摄取和积聚增加。单纯性脂肪变性可能进展为伴有炎症、肝细胞损伤和纤维化的非酒精性脂肪性肝炎（NASH）。CCN1 是一种重要的基质蛋白，可调节细胞死亡并促进免疫细胞黏附，可能潜在地控制这一过程。CCN1 在 NASH 中的作用尚不清楚。我们研究了 CCN1 在脂肪性肝炎发病机制中的作用。发现 CCN1 的上调与 NASH 患者、肥胖小鼠和 FFA 处理的肝细胞模型中的脂肪变性密切相关。在小鼠 NASH 模型中控制 CCN1 的表达表明，CCN1 增加了脂肪变性和炎症的严重程度。从序列结果来看，我们发现与对照相比，在过表达 CCN1 的 MCD 小鼠中，脂肪酸代谢基因主要参与。然后，使用定制的基于通路的 qPCR 基因表达谱芯片检测脂肪酸代谢基因的表达。表达分析表明，CCN1 过表达显著上调了脂肪酸代谢相关基因的表达。体外分析显示，CCN1 在脂肪变性模型中增加了小鼠原代肝细胞中的细胞内 TG 含量、促炎细胞因子和凋亡相关蛋白的表达水平。我们确定 CCN1 是非酒精性脂肪性肝炎（NASH）的一个重要正向调节因子。
