Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells.
Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells.
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DOI：
10.1038/s41598-017-03389-2
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发表时间：
2017-06-16
影响因子：
4.6
通讯作者：
Byun KS
中科院分区：
文献类型：
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作者：
Lee YS;Kim SY;Ko E;Lee JH;Yi HS;Yoo YJ;Je J;Suh SJ;Jung YK;Kim JH;Seo YS;Yim HJ;Jeong WI;Yeon JE;Um SH;Byun KS
非酒精性脂肪性肝病（NAFLD）是慢性肝病的主要病因，但从单纯性脂肪变性发展为非酒精性脂肪性肝炎（NASH）的确切机制尚不清楚。在这里，我们研究了外泌体在NAFLD进展中的作用。从经棕榈酸处理的人肝癌细胞系中分离出外泌体，并用微阵列检测其miRNA谱。然后用肝细胞分离的外泌体处理人肝星状细胞（HSC）系（LX-2）。与对照组相比，pa处理的肝细胞显示CD36和外泌体的产生显著增加。微阵列分析显示，在载体和pa处理的肝细胞外泌体之间存在不同的miRNA表达模式。当LX-2细胞与来自pa处理的肝细胞的外泌体一起培养时，与来自载体处理的肝细胞的外泌体相比，与纤维化发生相关的基因表达显著扩增。综上所述，PA处理增强了这些肝细胞外泌体的产生，并改变了它们的外泌体miRNA谱。此外，来自pa处理的肝细胞的外泌体引起造血干细胞中纤维化基因表达水平的增加。因此，外泌体可能在肝细胞和hsc之间的串扰中发挥重要作用，在单纯脂肪变性到NASH的过程中。
Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes. Compared with controls, PA-treated hepatocytes displayed significantly increased CD36 and exosome production. The microarray analysis showed there to be distinctive miRNA expression patterns between exosomes from vehicle- and PA-treated hepatocytes. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with exosomes from vehicle-treated hepatocytes. In conclusion, PA treatment enhanced the production of exosomes in these hepatocytes and changed their exosomal miRNA profile. Moreover, exosomes derived from PA-treated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs. Therefore, exosomes may have important roles in the crosstalk between hepatocytes and HSCs in the progression from simple steatosis to NASH.