CCN1可促进非酒精性脂肪性肝炎的肝脂肪变性和炎症。,Scientific Reports

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CCN1可促进非酒精性脂肪性肝炎的肝脂肪变性和炎症。
Scientific Reports ( IF 3.8 ) Pub Date : 2020-02-21 , DOI: 10.1038/s41598-020-60138-8
Linling Ju ₁ , Yan Sun ₂ , Hong Xue ₃ , Lin Chen ₁ , Chunyan Gu ₄ , Jianguo Shao ₁ , Rujian Lu ₅ , Xi Luo ₁ , Jue Wei ₆ , Xiong Ma ₇ , Zhaolian Bian ₁

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非酒精性脂肪肝疾病（NAFLD）的特征是肝细胞中脂质的摄取和积累增加。简单脂肪变性可能发展为非酒精性脂肪性肝炎（NASH），并伴有炎症，肝细胞损伤和纤维化。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粘附，并可能控制这一过程。CCN1在NASH中的作用仍不清楚。我们调查了CCN1在脂肪性肝炎发病机制中的作用。在NASH，肥胖小鼠和FFA处理的肝细胞模型中，发现CCN1上调与脂肪变性密切相关。控制小鼠NASH模型中CCN1的表达表明CCN1增加了脂肪变性和炎症的严重性。根据序列结果，我们发现与对照组相比，脂肪酸代谢基因主要参与过表达CCN1的MCD小鼠。然后，使用定制设计的基于途径的基于qPCR的基因表达阵列确定脂肪酸代谢基因的表达。表达分析表明，CCN1过表达显着上调了脂肪酸代谢相关基因的表达。体外分析显示，在使用鼠原代肝细胞的脂肪变性模型中，CCN1增加了细胞内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NASH中重要的正调控因子。使用定制设计的基于途径的基于qPCR的基因表达阵列确定脂肪酸代谢基因的表达。表达分析表明，CCN1过表达显着上调了脂肪酸代谢相关基因的表达。体外分析显示，在使用鼠原代肝细胞的脂肪变性模型中，CCN1增加了细胞内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NASH中重要的正调控因子。使用定制设计的基于途径的基于qPCR的基因表达阵列确定脂肪酸代谢基因的表达。表达分析表明，CCN1过表达显着上调了脂肪酸代谢相关基因的表达。体外分析显示，在使用鼠原代肝细胞的脂肪变性模型中，CCN1增加了细胞内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NASH中重要的正调控因子。鼠原代肝细胞在脂肪变性模型中的促炎细胞因子和凋亡相关蛋白的表达水平我们确定CCN1是NASH中重要的正调控因子。鼠原代肝细胞在脂肪变性模型中的促炎细胞因子和凋亡相关蛋白的表达水平我们确定CCN1是NASH中重要的正调节剂。

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CCN1 promotes hepatic steatosis and inflammation in non-alcoholic steatohepatitis.

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.

更新日期：2020-02-21

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