Abstract
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.
Highlights
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
Determining the exact mechanisms that lead to NAFLD and NASH is important for disease identification and the development of therapeutics
We found that palmitic acid (PA) treatment of hepatocytes increases the production of
Summary
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. Exosomes derived from PAtreated hepatocytes caused an increase in the expression levels of fibrotic genes in HSCs. exosomes may have important roles in the crosstalk between hepatocytes and HSCs in the progression from simple steatosis to NASH. Several factors were introduced to explain NASH aggravation, such as gut-derived bacterial toxins, adiponectin imbalance, oxidative stress, activation of hepatic stellate cells (HSCs), and activation of pro-fibrotic and pro-inflammatory factors[7] It is still unclear which factors are the most important in the development of the more aggressive diseases, such as NASH, cirrhosis, and HCC. Specific cargo molecules carried by exosomes are utilized for intercellular signal transduction Among these molecules, small non-coding microRNAs (miRNA) have important epigenetic functions, post-transcriptionally regulating gene expression. In NAFLD, any inter-cellular signal transduction through exosomes and miRNA has not been examined
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