TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice

Abstract Hepatocyte death, as well as the following inflammatory and fibrogenic signaling cascades, is the key trigger of liver fibrosis. Here, we isolated hepatocytes from CCl4-induced fibrotic liver and found that hepatocyte lincRNA-p21 significantly increased during liver fibrosis. The increase o...

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Autores principales:	Xiaolong Tu, Yuanyuan Zhang, Xiuxiu Zheng, Jia Deng, Huanan Li, Zhiqian Kang, Zhipeng Cao, Zhen Huang, Zhi Ding, Lei Dong, Jiangning Chen, Yuhui Zang, Junfeng Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70ce8021694d4e498c58905a70720ed8
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spelling	oai:doaj.org-article:70ce8021694d4e498c58905a70720ed82021-12-02T15:05:06ZTGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice10.1038/s41598-017-03175-02045-2322https://doaj.org/article/70ce8021694d4e498c58905a70720ed82017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03175-0https://doaj.org/toc/2045-2322Abstract Hepatocyte death, as well as the following inflammatory and fibrogenic signaling cascades, is the key trigger of liver fibrosis. Here, we isolated hepatocytes from CCl4-induced fibrotic liver and found that hepatocyte lincRNA-p21 significantly increased during liver fibrosis. The increase of hepatocyte lincRNA-p21 was associated with the loss of miR-30, which can inhibit TGF-β signaling by targeting KLF11. We revealed that lincRNA-p21 modulated miR-30 availability by acting as a competing endogenous RNA (ceRNA). The physiological significance of this interaction is highlighted by the feedback loop, in which lincRNA-p21 works as a downstream effector of the TGF-β signaling to strengthen TGF-β signaling and mediate its role in promoting liver fibrosis by interacting with miR-30. In vivo results showed that knockdown of hepatocyte lincRNA-p21 greatly reduced CCl4-induced liver fibrosis and inflammation, whereas ectopic expression of miR-30 in hepatocyte exhibited the similar results. Mechanistic studies further revealed that inhibition of miR-30 impaired the effects of lincRNA-p21 on liver fibrosis. Additionally, lincRNA-p21 promoted hepatocyte apoptosis in vitro and in vivo, whereas the proliferation rate of hepatocyte was suppressed by lincRNA-p21. The pleiotropic roles of hepatocyte lincRNA-p21 suggest that it may represent an unknown paradigm in liver fibrosis and serve as a potential target for therapy.Xiaolong TuYuanyuan ZhangXiuxiu ZhengJia DengHuanan LiZhiqian KangZhipeng CaoZhen HuangZhi DingLei DongJiangning ChenYuhui ZangJunfeng ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaolong Tu Yuanyuan Zhang Xiuxiu Zheng Jia Deng Huanan Li Zhiqian Kang Zhipeng Cao Zhen Huang Zhi Ding Lei Dong Jiangning Chen Yuhui Zang Junfeng Zhang TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice
description	Abstract Hepatocyte death, as well as the following inflammatory and fibrogenic signaling cascades, is the key trigger of liver fibrosis. Here, we isolated hepatocytes from CCl4-induced fibrotic liver and found that hepatocyte lincRNA-p21 significantly increased during liver fibrosis. The increase of hepatocyte lincRNA-p21 was associated with the loss of miR-30, which can inhibit TGF-β signaling by targeting KLF11. We revealed that lincRNA-p21 modulated miR-30 availability by acting as a competing endogenous RNA (ceRNA). The physiological significance of this interaction is highlighted by the feedback loop, in which lincRNA-p21 works as a downstream effector of the TGF-β signaling to strengthen TGF-β signaling and mediate its role in promoting liver fibrosis by interacting with miR-30. In vivo results showed that knockdown of hepatocyte lincRNA-p21 greatly reduced CCl4-induced liver fibrosis and inflammation, whereas ectopic expression of miR-30 in hepatocyte exhibited the similar results. Mechanistic studies further revealed that inhibition of miR-30 impaired the effects of lincRNA-p21 on liver fibrosis. Additionally, lincRNA-p21 promoted hepatocyte apoptosis in vitro and in vivo, whereas the proliferation rate of hepatocyte was suppressed by lincRNA-p21. The pleiotropic roles of hepatocyte lincRNA-p21 suggest that it may represent an unknown paradigm in liver fibrosis and serve as a potential target for therapy.
format	article
author	Xiaolong Tu Yuanyuan Zhang Xiuxiu Zheng Jia Deng Huanan Li Zhiqian Kang Zhipeng Cao Zhen Huang Zhi Ding Lei Dong Jiangning Chen Yuhui Zang Junfeng Zhang
author_facet	Xiaolong Tu Yuanyuan Zhang Xiuxiu Zheng Jia Deng Huanan Li Zhiqian Kang Zhipeng Cao Zhen Huang Zhi Ding Lei Dong Jiangning Chen Yuhui Zang Junfeng Zhang
author_sort	Xiaolong Tu
title	TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice
title_short	TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice
title_full	TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice
title_fullStr	TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice
title_full_unstemmed	TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice
title_sort	tgf-β-induced hepatocyte lincrna-p21 contributes to liver fibrosis in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/70ce8021694d4e498c58905a70720ed8
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TGF-β-induced hepatocyte lincRNA-p21 contributes to liver fibrosis in mice

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