Cargando…
Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway
Evidence shows that the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) is associated with activation of hepatic stellate cells (HSCs) and liver fibrosis in animal and in vitro studies. However, its roles in human liver fibrosis and the underlying mechanism in...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882958/ https://www.ncbi.nlm.nih.gov/pubmed/35237178 http://dx.doi.org/10.3389/fphys.2022.792182 |
_version_ | 1784659812410195968 |
---|---|
author | Wang, Tianqi Zhang, Chong Meng, Xiaoming Zhu, Benshuai Wang, Siyu Yuan, Wenkang Zhang, Sumei Xu, Jiegou Zhang, Chao |
author_facet | Wang, Tianqi Zhang, Chong Meng, Xiaoming Zhu, Benshuai Wang, Siyu Yuan, Wenkang Zhang, Sumei Xu, Jiegou Zhang, Chao |
author_sort | Wang, Tianqi |
collection | PubMed |
description | Evidence shows that the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) is associated with activation of hepatic stellate cells (HSCs) and liver fibrosis in animal and in vitro studies. However, its roles in human liver fibrosis and the underlying mechanism in HSC activation are not yet defined. In our current study, the expression of Lnc-MALAT1 in the fibrotic liver tissues and in the plasma extracelllar vesicles (EVs) of liver fibrosis patients was detected by FISH and qRT-PCR. The results revealed that enhanced expression of Lnc-MALAT1 was co-localized with increased expression of the fibrotic markers (collagen I and α-SMA) and the Wnt/β-catenin signaling proteins (β-catenin, cyclinD1 and c-myc) in the fibrotic liver tissues. The level of Lnc-MALAT1 in the plasma EVs isolated from 60 liver fibrosis patients was significantly increased compared with that of the 46 control patients, and area under receiver operating curve (AUROC) analysis showed that plasma EVs-Lnc-MALAT1 was a potential diagnostic marker for liver fibrosis, especially for high liver fibrosis. Plasma EVs with highly expressed Lnc-MALAT1 derived from high liver fibrosis patients up-regulated the expression of the fibrotic markers and enhanced the Wnt/β-catenin signaling in human hepatic stellate cells LX-2, and the fibrogenic effects in LX-2 were inhibited by Lnc-MALAT1 knock-down. Interestingly, TGF-β1, a potent pro-fibrotic cytokine, promoted the expression of Lnc-MALAT1 in LX-2 and its pro-fibrotic effects were also abolished by siRNA for Lnc-MALAT1, suggesting that Lnc-MALAT1 probably functions as a common mediator in the activation and fibrogenesis of HSCs. Our results indicate that enhanced expression of Lnc-MALAT1 in the fibrotic liver stimulate the activation of HSCs and thus promote their fibrogenic activity. These results also provide evidences that Lnc-MALAT1 is a potential therapeutic target and plasma EVs-Lnc-MALAT1 is a potential diagnostic biomarker for liver fibrosis. |
format | Online Article Text |
id | pubmed-8882958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88829582022-03-01 Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway Wang, Tianqi Zhang, Chong Meng, Xiaoming Zhu, Benshuai Wang, Siyu Yuan, Wenkang Zhang, Sumei Xu, Jiegou Zhang, Chao Front Physiol Physiology Evidence shows that the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) is associated with activation of hepatic stellate cells (HSCs) and liver fibrosis in animal and in vitro studies. However, its roles in human liver fibrosis and the underlying mechanism in HSC activation are not yet defined. In our current study, the expression of Lnc-MALAT1 in the fibrotic liver tissues and in the plasma extracelllar vesicles (EVs) of liver fibrosis patients was detected by FISH and qRT-PCR. The results revealed that enhanced expression of Lnc-MALAT1 was co-localized with increased expression of the fibrotic markers (collagen I and α-SMA) and the Wnt/β-catenin signaling proteins (β-catenin, cyclinD1 and c-myc) in the fibrotic liver tissues. The level of Lnc-MALAT1 in the plasma EVs isolated from 60 liver fibrosis patients was significantly increased compared with that of the 46 control patients, and area under receiver operating curve (AUROC) analysis showed that plasma EVs-Lnc-MALAT1 was a potential diagnostic marker for liver fibrosis, especially for high liver fibrosis. Plasma EVs with highly expressed Lnc-MALAT1 derived from high liver fibrosis patients up-regulated the expression of the fibrotic markers and enhanced the Wnt/β-catenin signaling in human hepatic stellate cells LX-2, and the fibrogenic effects in LX-2 were inhibited by Lnc-MALAT1 knock-down. Interestingly, TGF-β1, a potent pro-fibrotic cytokine, promoted the expression of Lnc-MALAT1 in LX-2 and its pro-fibrotic effects were also abolished by siRNA for Lnc-MALAT1, suggesting that Lnc-MALAT1 probably functions as a common mediator in the activation and fibrogenesis of HSCs. Our results indicate that enhanced expression of Lnc-MALAT1 in the fibrotic liver stimulate the activation of HSCs and thus promote their fibrogenic activity. These results also provide evidences that Lnc-MALAT1 is a potential therapeutic target and plasma EVs-Lnc-MALAT1 is a potential diagnostic biomarker for liver fibrosis. Frontiers Media S.A. 2022-02-14 /pmc/articles/PMC8882958/ /pubmed/35237178 http://dx.doi.org/10.3389/fphys.2022.792182 Text en Copyright © 2022 Wang, Zhang, Meng, Zhu, Wang, Yuan, Zhang, Xu and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Wang, Tianqi Zhang, Chong Meng, Xiaoming Zhu, Benshuai Wang, Siyu Yuan, Wenkang Zhang, Sumei Xu, Jiegou Zhang, Chao Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway |
title | Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway |
title_full | Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway |
title_fullStr | Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway |
title_full_unstemmed | Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway |
title_short | Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Extracellular Vesicles Promotes Hepatic Stellate Cell Activation, Liver Fibrosis and β-Catenin Signaling Pathway |
title_sort | long noncoding rna metastasis-associated lung adenocarcinoma transcript 1 in extracellular vesicles promotes hepatic stellate cell activation, liver fibrosis and β-catenin signaling pathway |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882958/ https://www.ncbi.nlm.nih.gov/pubmed/35237178 http://dx.doi.org/10.3389/fphys.2022.792182 |
work_keys_str_mv | AT wangtianqi longnoncodingrnametastasisassociatedlungadenocarcinomatranscript1inextracellularvesiclespromoteshepaticstellatecellactivationliverfibrosisandbcateninsignalingpathway AT zhangchong longnoncodingrnametastasisassociatedlungadenocarcinomatranscript1inextracellularvesiclespromoteshepaticstellatecellactivationliverfibrosisandbcateninsignalingpathway AT mengxiaoming longnoncodingrnametastasisassociatedlungadenocarcinomatranscript1inextracellularvesiclespromoteshepaticstellatecellactivationliverfibrosisandbcateninsignalingpathway AT zhubenshuai longnoncodingrnametastasisassociatedlungadenocarcinomatranscript1inextracellularvesiclespromoteshepaticstellatecellactivationliverfibrosisandbcateninsignalingpathway AT wangsiyu longnoncodingrnametastasisassociatedlungadenocarcinomatranscript1inextracellularvesiclespromoteshepaticstellatecellactivationliverfibrosisandbcateninsignalingpathway AT yuanwenkang longnoncodingrnametastasisassociatedlungadenocarcinomatranscript1inextracellularvesiclespromoteshepaticstellatecellactivationliverfibrosisandbcateninsignalingpathway AT zhangsumei longnoncodingrnametastasisassociatedlungadenocarcinomatranscript1inextracellularvesiclespromoteshepaticstellatecellactivationliverfibrosisandbcateninsignalingpathway AT xujiegou longnoncodingrnametastasisassociatedlungadenocarcinomatranscript1inextracellularvesiclespromoteshepaticstellatecellactivationliverfibrosisandbcateninsignalingpathway AT zhangchao longnoncodingrnametastasisassociatedlungadenocarcinomatranscript1inextracellularvesiclespromoteshepaticstellatecellactivationliverfibrosisandbcateninsignalingpathway |