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Sci Rep. 2017 Jun 16;7(1):3710. doi: 10.1038/s41598-017-03389-2.

Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells.

Author information

1
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
2
Lab of Liver Research, Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
3
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
4
Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, 305-764, Republic of Korea.
5
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. jeyyeon@hotmail.com.

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.

PMID:
28623272
PMCID:
PMC5473841
DOI:
10.1038/s41598-017-03389-2
[Indexed for MEDLINE]
Free PMC Article

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