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

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 isolate...

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Autores principales: Young-Sun Lee, So Yeon Kim, Eunjung Ko, Jun-Hee Lee, Hyon-Seung Yi, Yang Jae Yoo, Jihye Je, Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Won-Il Jeong, Jong Eun Yeon, Soon Ho Um, Kwan Soo Byun
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:fc2211e42e4b41eeac53d974a0fc5a602021-12-02T12:32:19ZExosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells10.1038/s41598-017-03389-22045-2322https://doaj.org/article/fc2211e42e4b41eeac53d974a0fc5a602017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03389-2https://doaj.org/toc/2045-2322Abstract 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.Young-Sun LeeSo Yeon KimEunjung KoJun-Hee LeeHyon-Seung YiYang Jae YooJihye JeSang Jun SuhYoung Kul JungJi Hoon KimYeon Seok SeoHyung Joon YimWon-Il JeongJong Eun YeonSoon Ho UmKwan Soo ByunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Young-Sun Lee
So Yeon Kim
Eunjung Ko
Jun-Hee Lee
Hyon-Seung Yi
Yang Jae Yoo
Jihye Je
Sang Jun Suh
Young Kul Jung
Ji Hoon Kim
Yeon Seok Seo
Hyung Joon Yim
Won-Il Jeong
Jong Eun Yeon
Soon Ho Um
Kwan Soo Byun
Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
description 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.
format article
author Young-Sun Lee
So Yeon Kim
Eunjung Ko
Jun-Hee Lee
Hyon-Seung Yi
Yang Jae Yoo
Jihye Je
Sang Jun Suh
Young Kul Jung
Ji Hoon Kim
Yeon Seok Seo
Hyung Joon Yim
Won-Il Jeong
Jong Eun Yeon
Soon Ho Um
Kwan Soo Byun
author_facet Young-Sun Lee
So Yeon Kim
Eunjung Ko
Jun-Hee Lee
Hyon-Seung Yi
Yang Jae Yoo
Jihye Je
Sang Jun Suh
Young Kul Jung
Ji Hoon Kim
Yeon Seok Seo
Hyung Joon Yim
Won-Il Jeong
Jong Eun Yeon
Soon Ho Um
Kwan Soo Byun
author_sort Young-Sun Lee
title Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
title_short Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
title_full Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
title_fullStr Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
title_full_unstemmed Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
title_sort exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/fc2211e42e4b41eeac53d974a0fc5a60
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