MicroRNA-27a modulates HCV infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.

<h4>Background and aims</h4>Despite the discovery of hepatitis C virus (HCV) entry factor, the mechanism by which it is regulated by miRNAs remains unclear. Adipose tissue-derived human mesenchymal stem cells (AT-hMSCs) have been widely used for differentiated hepatocyte-like cells (DHCs...

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Autores principales:	Jung Eun Choi, Wonhee Hur, Jung-Hee Kim, Tian Zhu Li, Eun Byul Lee, Sung Won Lee, Wonseok Kang, Eui-Cheol Shin, Takaji Wakita, Seung Kew Yoon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7fd4ef43cec4f81804f806e1c73b33a
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spelling	oai:doaj.org-article:c7fd4ef43cec4f81804f806e1c73b33a2021-11-18T08:19:34ZMicroRNA-27a modulates HCV infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.1932-620310.1371/journal.pone.0091958https://doaj.org/article/c7fd4ef43cec4f81804f806e1c73b33a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24824429/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background and aims</h4>Despite the discovery of hepatitis C virus (HCV) entry factor, the mechanism by which it is regulated by miRNAs remains unclear. Adipose tissue-derived human mesenchymal stem cells (AT-hMSCs) have been widely used for differentiated hepatocyte-like cells (DHCs). Here, we established an in vitro HCV infection model using DHCs from AT-hMSCs and identified miRNAs that modulate HCV infectivity.<h4>Methods</h4>AT-hMSCs were differentiated into DHCs using the conditional media, and evaluated for hepatocyte characteristics using RT-PCR, immunocytochemistry, periodic acid-Schiff staining, and a urea synthesis assay. The expression of HCV candidate receptors was also verified using immunocytochemistry. The levels of candidate miRNAs targeting HCV receptors were then determined by relative quantitative RT-PCR (rqRT-PCR). Finally, DHCs were infected using HCVcc and serum from HCV-infected patients, and infectivity of the virus was measured by rqRT-PCR and transmission electron microscopy (TEM).<h4>Results</h4>The expected changes in morphology, function and hepatic gene expression were observed during hepatic differentiation. Moreover, the expression of candidate HCV entry factors and miR-27a were altered during hepatic differentiation. The infection and replication of HCV occurred efficiently in DHCs treated with HCVcc or infected with serum from HCV-infected patients. In addition, HCV infectivity was suppressed in miR-27a-transfected DHCs, due to the inhibition of LDLR expression by miR-27a.<h4>Conclusions</h4>Our results demonstrate that AT-hMSCs are a good source of DHCs, which are suitable for in vitro cultivation of HCV. Furthermore, these results suggest that miR-27a modulates HCV infectivity by regulating LDLR expression.Jung Eun ChoiWonhee HurJung-Hee KimTian Zhu LiEun Byul LeeSung Won LeeWonseok KangEui-Cheol ShinTakaji WakitaSeung Kew YoonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e91958 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jung Eun Choi Wonhee Hur Jung-Hee Kim Tian Zhu Li Eun Byul Lee Sung Won Lee Wonseok Kang Eui-Cheol Shin Takaji Wakita Seung Kew Yoon MicroRNA-27a modulates HCV infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.
description	<h4>Background and aims</h4>Despite the discovery of hepatitis C virus (HCV) entry factor, the mechanism by which it is regulated by miRNAs remains unclear. Adipose tissue-derived human mesenchymal stem cells (AT-hMSCs) have been widely used for differentiated hepatocyte-like cells (DHCs). Here, we established an in vitro HCV infection model using DHCs from AT-hMSCs and identified miRNAs that modulate HCV infectivity.<h4>Methods</h4>AT-hMSCs were differentiated into DHCs using the conditional media, and evaluated for hepatocyte characteristics using RT-PCR, immunocytochemistry, periodic acid-Schiff staining, and a urea synthesis assay. The expression of HCV candidate receptors was also verified using immunocytochemistry. The levels of candidate miRNAs targeting HCV receptors were then determined by relative quantitative RT-PCR (rqRT-PCR). Finally, DHCs were infected using HCVcc and serum from HCV-infected patients, and infectivity of the virus was measured by rqRT-PCR and transmission electron microscopy (TEM).<h4>Results</h4>The expected changes in morphology, function and hepatic gene expression were observed during hepatic differentiation. Moreover, the expression of candidate HCV entry factors and miR-27a were altered during hepatic differentiation. The infection and replication of HCV occurred efficiently in DHCs treated with HCVcc or infected with serum from HCV-infected patients. In addition, HCV infectivity was suppressed in miR-27a-transfected DHCs, due to the inhibition of LDLR expression by miR-27a.<h4>Conclusions</h4>Our results demonstrate that AT-hMSCs are a good source of DHCs, which are suitable for in vitro cultivation of HCV. Furthermore, these results suggest that miR-27a modulates HCV infectivity by regulating LDLR expression.
format	article
author	Jung Eun Choi Wonhee Hur Jung-Hee Kim Tian Zhu Li Eun Byul Lee Sung Won Lee Wonseok Kang Eui-Cheol Shin Takaji Wakita Seung Kew Yoon
author_facet	Jung Eun Choi Wonhee Hur Jung-Hee Kim Tian Zhu Li Eun Byul Lee Sung Won Lee Wonseok Kang Eui-Cheol Shin Takaji Wakita Seung Kew Yoon
author_sort	Jung Eun Choi
title	MicroRNA-27a modulates HCV infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.
title_short	MicroRNA-27a modulates HCV infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.
title_full	MicroRNA-27a modulates HCV infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.
title_fullStr	MicroRNA-27a modulates HCV infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.
title_full_unstemmed	MicroRNA-27a modulates HCV infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.
title_sort	microrna-27a modulates hcv infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/c7fd4ef43cec4f81804f806e1c73b33a
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MicroRNA-27a modulates HCV infection in differentiated hepatocyte-like cells from adipose tissue-derived mesenchymal stem cells.

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