Effect of miR-183-5p on Cholestatic Liver Fibrosis by Regulating Fork Head Box Protein O1 Expression

Liver fibrosis is a common pathological feature of end-stage liver disease and has no effective treatment. MicroRNAs (miRNAs) have been found to modulate gene expression in liver disease. But the potential role of miRNA in hepatic fibrosis is still unclear. The objective of this research is to study...

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Autores principales:	Yongxin Wang, Bin Chen, Chengcheng Xiao, Jiang Yu, Xiangyang Bu, Fengxing Jiang, Weijie Ding, Zhong Ge
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	liver fibrosis miR-183-5p FOXO1 hepatic stellate cell TGF-β pathway Physiology QP1-981
Acceso en línea:	https://doaj.org/article/c564c3580d254a9c919da5f3323b9d4e
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spelling	oai:doaj.org-article:c564c3580d254a9c919da5f3323b9d4e2021-11-18T09:10:14ZEffect of miR-183-5p on Cholestatic Liver Fibrosis by Regulating Fork Head Box Protein O1 Expression1664-042X10.3389/fphys.2021.737313https://doaj.org/article/c564c3580d254a9c919da5f3323b9d4e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.737313/fullhttps://doaj.org/toc/1664-042XLiver fibrosis is a common pathological feature of end-stage liver disease and has no effective treatment. MicroRNAs (miRNAs) have been found to modulate gene expression in liver disease. But the potential role of miRNA in hepatic fibrosis is still unclear. The objective of this research is to study the potential mechanism and biological function of miR-183-5p in liver fibrosis. In this study, we used high-throughput sequencing to find that miR-183-5p is upregulated in human fibrotic liver tissues. In addition, miR-183-5p was upregulated both in rat liver fibrosis tissue induced by bile-duct ligation (BDL) and activated LX-2 cells (human hepatic stellate cell line) according to the result of quantitative real-time PCR (RT-qPCR). Moreover, the inhibition of miR-183-5p alleviated liver fibrosis, decreased the fibrotic biomarker levels in vitro and in vivo, and led toLX-2 cell proliferation inhibition and, apoptosis induction. The result of dual-luciferase assay revealed that miR-183-5p suppressed fork head box protein O1 (FOXO1) expression by binding to its 3′UTR directly. Next, we used lentivirus to overexpress FOXO1 in LX-2 cells, and we found that overexpression of FOXO1 reversed the promotion of miR-183-5p on liver fibrosis, reducing the fibrotic biomarker levels inLX-2 cells, inhibitingLX-2 cell proliferation, and promoting apoptosis. Furthermore, overexpression of FOXO1 prevented the activation of the transforming growth factor (TGF)-β signaling pathway in TGF-β1-induced LX-2 cells according to the result of western blotting. In conclusion, the findings showed thatmiR-183-5p might act as a key regulator of liver fibrosis, and miR-183-5p could promote cholestatic liver fibrosis by inhibiting FOXO1 expression through the TGF-β signaling pathway. Thus, inhibition of miR-183-5pmay be a new way to prevent and improve liver fibrosis.Yongxin WangBin ChenChengcheng XiaoJiang YuXiangyang BuFengxing JiangWeijie DingZhong GeFrontiers Media S.A.articleliver fibrosismiR-183-5pFOXO1hepatic stellate cellTGF-β pathwayPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	liver fibrosis miR-183-5p FOXO1 hepatic stellate cell TGF-β pathway Physiology QP1-981
spellingShingle	liver fibrosis miR-183-5p FOXO1 hepatic stellate cell TGF-β pathway Physiology QP1-981 Yongxin Wang Bin Chen Chengcheng Xiao Jiang Yu Xiangyang Bu Fengxing Jiang Weijie Ding Zhong Ge Effect of miR-183-5p on Cholestatic Liver Fibrosis by Regulating Fork Head Box Protein O1 Expression
description	Liver fibrosis is a common pathological feature of end-stage liver disease and has no effective treatment. MicroRNAs (miRNAs) have been found to modulate gene expression in liver disease. But the potential role of miRNA in hepatic fibrosis is still unclear. The objective of this research is to study the potential mechanism and biological function of miR-183-5p in liver fibrosis. In this study, we used high-throughput sequencing to find that miR-183-5p is upregulated in human fibrotic liver tissues. In addition, miR-183-5p was upregulated both in rat liver fibrosis tissue induced by bile-duct ligation (BDL) and activated LX-2 cells (human hepatic stellate cell line) according to the result of quantitative real-time PCR (RT-qPCR). Moreover, the inhibition of miR-183-5p alleviated liver fibrosis, decreased the fibrotic biomarker levels in vitro and in vivo, and led toLX-2 cell proliferation inhibition and, apoptosis induction. The result of dual-luciferase assay revealed that miR-183-5p suppressed fork head box protein O1 (FOXO1) expression by binding to its 3′UTR directly. Next, we used lentivirus to overexpress FOXO1 in LX-2 cells, and we found that overexpression of FOXO1 reversed the promotion of miR-183-5p on liver fibrosis, reducing the fibrotic biomarker levels inLX-2 cells, inhibitingLX-2 cell proliferation, and promoting apoptosis. Furthermore, overexpression of FOXO1 prevented the activation of the transforming growth factor (TGF)-β signaling pathway in TGF-β1-induced LX-2 cells according to the result of western blotting. In conclusion, the findings showed thatmiR-183-5p might act as a key regulator of liver fibrosis, and miR-183-5p could promote cholestatic liver fibrosis by inhibiting FOXO1 expression through the TGF-β signaling pathway. Thus, inhibition of miR-183-5pmay be a new way to prevent and improve liver fibrosis.
format	article
author	Yongxin Wang Bin Chen Chengcheng Xiao Jiang Yu Xiangyang Bu Fengxing Jiang Weijie Ding Zhong Ge
author_facet	Yongxin Wang Bin Chen Chengcheng Xiao Jiang Yu Xiangyang Bu Fengxing Jiang Weijie Ding Zhong Ge
author_sort	Yongxin Wang
title	Effect of miR-183-5p on Cholestatic Liver Fibrosis by Regulating Fork Head Box Protein O1 Expression
title_short	Effect of miR-183-5p on Cholestatic Liver Fibrosis by Regulating Fork Head Box Protein O1 Expression
title_full	Effect of miR-183-5p on Cholestatic Liver Fibrosis by Regulating Fork Head Box Protein O1 Expression
title_fullStr	Effect of miR-183-5p on Cholestatic Liver Fibrosis by Regulating Fork Head Box Protein O1 Expression
title_full_unstemmed	Effect of miR-183-5p on Cholestatic Liver Fibrosis by Regulating Fork Head Box Protein O1 Expression
title_sort	effect of mir-183-5p on cholestatic liver fibrosis by regulating fork head box protein o1 expression
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c564c3580d254a9c919da5f3323b9d4e
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Effect of miR-183-5p on Cholestatic Liver Fibrosis by Regulating Fork Head Box Protein O1 Expression

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