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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Vydané v:	Scientific reports Ročník 7; číslo 1; s. 3710 - 10
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 16.06.2017 Nature Publishing Group Nature Portfolio
Predmet:	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
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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.
AbstractList	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. 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. 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.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.
ArticleNumber	3710
Author	Jung, Young Kul Kim, Ji Hoon Seo, Yeon Seok Suh, Sang Jun Jeong, Won-Il Kim, So Yeon Lee, Young-Sun Lee, Jun-Hee Yi, Hyon-Seung Yim, Hyung Joon Byun, Kwan Soo Je, Jihye Yeon, Jong Eun Um, Soon Ho Ko, Eunjung Yoo, Yang Jae
Author_xml	– sequence: 1 givenname: Young-Sun orcidid: 0000-0001-6396-0859 surname: Lee fullname: Lee, Young-Sun organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 2 givenname: So Yeon orcidid: 0000-0003-1319-6164 surname: Kim fullname: Kim, So Yeon organization: Lab of Liver Research, Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST) – sequence: 3 givenname: Eunjung surname: Ko fullname: Ko, Eunjung organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 4 givenname: Jun-Hee surname: Lee fullname: Lee, Jun-Hee organization: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST) – sequence: 5 givenname: Hyon-Seung surname: Yi fullname: Yi, Hyon-Seung organization: Department of Internal Medicine, Chungnam National University School of Medicine – sequence: 6 givenname: Yang Jae surname: Yoo fullname: Yoo, Yang Jae organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 7 givenname: Jihye surname: Je fullname: Je, Jihye organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 8 givenname: Sang Jun surname: Suh fullname: Suh, Sang Jun organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 9 givenname: Young Kul surname: Jung fullname: Jung, Young Kul organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 10 givenname: Ji Hoon surname: Kim fullname: Kim, Ji Hoon organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 11 givenname: Yeon Seok surname: Seo fullname: Seo, Yeon Seok organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 12 givenname: Hyung Joon surname: Yim fullname: Yim, Hyung Joon organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 13 givenname: Won-Il surname: Jeong fullname: Jeong, Won-Il organization: Lab of Liver Research, Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST) – sequence: 14 givenname: Jong Eun surname: Yeon fullname: Yeon, Jong Eun email: jeyyeon@hotmail.com organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 15 givenname: Soon Ho surname: Um fullname: Um, Soon Ho organization: Department of Internal Medicine, Korea University College of Medicine – sequence: 16 givenname: Kwan Soo surname: Byun fullname: Byun, Kwan Soo organization: Department of Internal Medicine, Korea University College of Medicine
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/28623272$$D View this record in MEDLINE/PubMed
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Snippet	Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to... Abstract Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis...
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Title	Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
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