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Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells
Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic viral hepatitis and, more recently, from fatty liver diseases. Activation and proliferation of hepatic stellate cells (HSCs) represent a key aspect of fibrogenesis and are associated with progressive reduction of HSC...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992517/ https://www.ncbi.nlm.nih.gov/pubmed/27579319 http://dx.doi.org/10.1155/2016/7478650 |
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author | Wu, Lin Mao, Chengqiong Ming, Xin |
author_facet | Wu, Lin Mao, Chengqiong Ming, Xin |
author_sort | Wu, Lin |
collection | PubMed |
description | Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic viral hepatitis and, more recently, from fatty liver diseases. Activation and proliferation of hepatic stellate cells (HSCs) represent a key aspect of fibrogenesis and are associated with progressive reduction of HSC apoptosis. Bcl-x, an antiapoptotic member of Bcl-2 gene family, plays a role in apoptosis regulation in mammalian cells. Through alternative splicing, the Bcl-x gene yields two major protein isoforms with opposing functions, antiapoptotic Bcl-x(L) and proapoptotic Bcl-x(S). This study aimed to investigate the role of Bcl-x and its alternate splicing in HSC apoptosis. The results indicated that the expression of Bcl-x(L) was dramatically higher than Bcl-2 in activated human HSCs. The relative expression of Bcl-x(L) over Bcl-x(S) increased gradually when HSCs were activated in cell culture, which was consistent with the increase in apoptosis resistance of activated HSCs. Redirection of Bcl-x splicing by an antisense oligonucleotide from the antiapoptotic isoform to the proapoptotic isoform induced death of HSCs without other apoptosis stimuli. We conclude that Bcl-x plays a role in regulation of HSC apoptosis and modulation of Bcl-x alternative splicing may become a novel molecular therapy for liver fibrosis. |
format | Online Article Text |
id | pubmed-4992517 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-49925172016-08-30 Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells Wu, Lin Mao, Chengqiong Ming, Xin Biomed Res Int Research Article Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic viral hepatitis and, more recently, from fatty liver diseases. Activation and proliferation of hepatic stellate cells (HSCs) represent a key aspect of fibrogenesis and are associated with progressive reduction of HSC apoptosis. Bcl-x, an antiapoptotic member of Bcl-2 gene family, plays a role in apoptosis regulation in mammalian cells. Through alternative splicing, the Bcl-x gene yields two major protein isoforms with opposing functions, antiapoptotic Bcl-x(L) and proapoptotic Bcl-x(S). This study aimed to investigate the role of Bcl-x and its alternate splicing in HSC apoptosis. The results indicated that the expression of Bcl-x(L) was dramatically higher than Bcl-2 in activated human HSCs. The relative expression of Bcl-x(L) over Bcl-x(S) increased gradually when HSCs were activated in cell culture, which was consistent with the increase in apoptosis resistance of activated HSCs. Redirection of Bcl-x splicing by an antisense oligonucleotide from the antiapoptotic isoform to the proapoptotic isoform induced death of HSCs without other apoptosis stimuli. We conclude that Bcl-x plays a role in regulation of HSC apoptosis and modulation of Bcl-x alternative splicing may become a novel molecular therapy for liver fibrosis. Hindawi Publishing Corporation 2016 2016-08-07 /pmc/articles/PMC4992517/ /pubmed/27579319 http://dx.doi.org/10.1155/2016/7478650 Text en Copyright © 2016 Lin Wu et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wu, Lin Mao, Chengqiong Ming, Xin Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells |
title | Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells |
title_full | Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells |
title_fullStr | Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells |
title_full_unstemmed | Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells |
title_short | Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells |
title_sort | modulation of bcl-x alternative splicing induces apoptosis of human hepatic stellate cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992517/ https://www.ncbi.nlm.nih.gov/pubmed/27579319 http://dx.doi.org/10.1155/2016/7478650 |
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