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

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...

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Bibliographic Details
Published in:Scientific reports Vol. 7; no. 1; pp. 3710 - 10
Main Authors: Lee, Young-Sun, Kim, So Yeon, Ko, Eunjung, Lee, Jun-Hee, Yi, Hyon-Seung, Yoo, Yang Jae, Je, Jihye, Suh, Sang Jun, Jung, Young Kul, Kim, Ji Hoon, Seo, Yeon Seok, Yim, Hyung Joon, Jeong, Won-Il, Yeon, Jong Eun, Um, Soon Ho, Byun, Kwan Soo
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 16.06.2017
Nature Publishing Group
Nature Portfolio
Subjects:
13/95
45/61
631/80/86/820
692/4020/4021/1607/2750
692/4020/4021/1607/2751
Animals
CD36 antigen
Cell Line, Tumor
Exosomes
Exosomes - metabolism
Exosomes - ultrastructure
Fatty liver
Fibrosis
Gene Expression Profiling
Hepatic Stellate Cells - metabolism
Hepatic Stellate Cells - ultrastructure
Hepatocytes
Hepatocytes - drug effects
Hepatocytes - metabolism
Hepatocytes - ultrastructure
Hepatoma
Humanities and Social Sciences
Humans
Liver cancer
Liver Cirrhosis - etiology
Liver Cirrhosis - metabolism
Liver diseases
Male
Mice
MicroRNAs - genetics
miRNA
multidisciplinary
Palmitic acid
Palmitic Acid - pharmacology
Science
Science (multidisciplinary)
Steatosis
Stellate cells
Transcriptome
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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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. 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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-03389-2