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The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition
Liver fibrosis leading to cirrhosis is one of the major health burdens worldwide with currently limited therapeutic options available. Long noncoding RNAs (lncRNAs) play important roles in various biological and pathological processes in a cell- or tissue-specific manner. However, there is still an...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831459/ https://www.ncbi.nlm.nih.gov/pubmed/31695787 http://dx.doi.org/10.7150/thno.36942 |
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author | Zhang, Kun Zhang, Mengxia Yao, Qingbin Han, Xiaohui Zhao, Yanmian Zheng, Lina Li, Guantong Liu, Qi Chang, Yanan Zhang, Peijun Cui, Hongmei Shi, Zhemin Chen, Ting Yao, Zhi Han, Tao Hong, Wei |
author_facet | Zhang, Kun Zhang, Mengxia Yao, Qingbin Han, Xiaohui Zhao, Yanmian Zheng, Lina Li, Guantong Liu, Qi Chang, Yanan Zhang, Peijun Cui, Hongmei Shi, Zhemin Chen, Ting Yao, Zhi Han, Tao Hong, Wei |
author_sort | Zhang, Kun |
collection | PubMed |
description | Liver fibrosis leading to cirrhosis is one of the major health burdens worldwide with currently limited therapeutic options available. Long noncoding RNAs (lncRNAs) play important roles in various biological and pathological processes in a cell- or tissue-specific manner. However, there is still an important gap in the understanding of the role of hepatocyte-specific lncRNAs in liver fibrosis. Methods: The expressions of lnc-Hser in human and mice fibrotic livers as well as primary hepatocytes (HCs) of mice developing liver fibrosis were determined by real-time RT-PCR. The roles and mechanisms of lnc-Hser in HCs and liver fibrosis were determined in vitro and in vivo. Results: In this study, we have identified a hepatocyte-specifically expressed lnc-Hser, which was reduced in human and mice fibrotic livers as well as primary HCs of mice developing liver fibrosis. We have shown that silencing lnc-Hser aggravated liver fibrosis both in vitro and in vivo through inducing the epithelial-mesenchymal transition (EMT) and the apoptosis of HCs. In addition, knockdown of lnc-Hser promoted hepatic stellate cells (HSCs) activation through the signals derived from injured HCs. Mechanistically, we have revealed that lnc-Hser inhibited HCs apoptosis via the C5AR1-Hippo-YAP pathway and suppressed HCs EMT via the Notch signaling. Conclusions: Our work has identified a hepatocyte-specific lnc-HSER that regulates liver fibrosis, providing a proof that this molecule is a novel biomarker for damaged HCs and a potential target for anti-fibrotic therapy. |
format | Online Article Text |
id | pubmed-6831459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-68314592019-11-06 The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition Zhang, Kun Zhang, Mengxia Yao, Qingbin Han, Xiaohui Zhao, Yanmian Zheng, Lina Li, Guantong Liu, Qi Chang, Yanan Zhang, Peijun Cui, Hongmei Shi, Zhemin Chen, Ting Yao, Zhi Han, Tao Hong, Wei Theranostics Research Paper Liver fibrosis leading to cirrhosis is one of the major health burdens worldwide with currently limited therapeutic options available. Long noncoding RNAs (lncRNAs) play important roles in various biological and pathological processes in a cell- or tissue-specific manner. However, there is still an important gap in the understanding of the role of hepatocyte-specific lncRNAs in liver fibrosis. Methods: The expressions of lnc-Hser in human and mice fibrotic livers as well as primary hepatocytes (HCs) of mice developing liver fibrosis were determined by real-time RT-PCR. The roles and mechanisms of lnc-Hser in HCs and liver fibrosis were determined in vitro and in vivo. Results: In this study, we have identified a hepatocyte-specifically expressed lnc-Hser, which was reduced in human and mice fibrotic livers as well as primary HCs of mice developing liver fibrosis. We have shown that silencing lnc-Hser aggravated liver fibrosis both in vitro and in vivo through inducing the epithelial-mesenchymal transition (EMT) and the apoptosis of HCs. In addition, knockdown of lnc-Hser promoted hepatic stellate cells (HSCs) activation through the signals derived from injured HCs. Mechanistically, we have revealed that lnc-Hser inhibited HCs apoptosis via the C5AR1-Hippo-YAP pathway and suppressed HCs EMT via the Notch signaling. Conclusions: Our work has identified a hepatocyte-specific lnc-HSER that regulates liver fibrosis, providing a proof that this molecule is a novel biomarker for damaged HCs and a potential target for anti-fibrotic therapy. Ivyspring International Publisher 2019-10-12 /pmc/articles/PMC6831459/ /pubmed/31695787 http://dx.doi.org/10.7150/thno.36942 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Zhang, Kun Zhang, Mengxia Yao, Qingbin Han, Xiaohui Zhao, Yanmian Zheng, Lina Li, Guantong Liu, Qi Chang, Yanan Zhang, Peijun Cui, Hongmei Shi, Zhemin Chen, Ting Yao, Zhi Han, Tao Hong, Wei The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition |
title | The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition |
title_full | The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition |
title_fullStr | The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition |
title_full_unstemmed | The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition |
title_short | The hepatocyte-specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition |
title_sort | hepatocyte-specifically expressed lnc-hser alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831459/ https://www.ncbi.nlm.nih.gov/pubmed/31695787 http://dx.doi.org/10.7150/thno.36942 |
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