Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target?
Chronic liver diseases (CLD) represent a worldwide health problem. While CLDs may have diverse etiologies, a common pathogenic denominator is the presence of liver fibrosis. Cirrhosis, the end-stage of CLD, is characterized by extensive fibrosis and is markedly associated with the development of hep...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/10/2321 |
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| author | Alex Claveria-Cabello Leticia Colyn Maria Arechederra Jesus M. Urman Carmen Berasain Matias A. Avila Maite G. Fernandez-Barrena |
| author_facet | Alex Claveria-Cabello Leticia Colyn Maria Arechederra Jesus M. Urman Carmen Berasain Matias A. Avila Maite G. Fernandez-Barrena |
| author_sort | Alex Claveria-Cabello |
| collection | DOAJ |
| description | Chronic liver diseases (CLD) represent a worldwide health problem. While CLDs may have diverse etiologies, a common pathogenic denominator is the presence of liver fibrosis. Cirrhosis, the end-stage of CLD, is characterized by extensive fibrosis and is markedly associated with the development of hepatocellular carcinoma. The most important event in hepatic fibrogenesis is the activation of hepatic stellate cells (HSC) following liver injury. Activated HSCs acquire a myofibroblast-like phenotype becoming proliferative, fibrogenic, and contractile cells. While transient activation of HSCs is part of the physiological mechanisms of tissue repair, protracted activation of a wound healing reaction leads to organ fibrosis. The phenotypic changes of activated HSCs involve epigenetic mechanisms mediated by non-coding RNAs (ncRNA) as well as by changes in DNA methylation and histone modifications. During CLD these epigenetic mechanisms become deregulated, with alterations in the expression and activity of epigenetic modulators. Here we provide an overview of the epigenetic alterations involved in fibrogenic HSCs transdifferentiation with particular focus on histones acetylation changes. We also discuss recent studies supporting the promising therapeutic potential of histone deacetylase inhibitors in liver fibrosis. |
| first_indexed | 2024-03-10T15:30:15Z |
| format | Article |
| id | doaj.art-18999c9f1d0c4f588307a584d85715e6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T15:30:15Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-18999c9f1d0c4f588307a584d85715e62023-11-20T17:41:38ZengMDPI AGCells2073-44092020-10-01910232110.3390/cells9102321Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target?Alex Claveria-Cabello0Leticia Colyn1Maria Arechederra2Jesus M. Urman3Carmen Berasain4Matias A. Avila5Maite G. Fernandez-Barrena6Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, SpainProgram of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, SpainProgram of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, SpainIdiSNA, Navarra Institute for Health Research, 31008 Pamplona, SpainProgram of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, SpainProgram of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, SpainProgram of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, SpainChronic liver diseases (CLD) represent a worldwide health problem. While CLDs may have diverse etiologies, a common pathogenic denominator is the presence of liver fibrosis. Cirrhosis, the end-stage of CLD, is characterized by extensive fibrosis and is markedly associated with the development of hepatocellular carcinoma. The most important event in hepatic fibrogenesis is the activation of hepatic stellate cells (HSC) following liver injury. Activated HSCs acquire a myofibroblast-like phenotype becoming proliferative, fibrogenic, and contractile cells. While transient activation of HSCs is part of the physiological mechanisms of tissue repair, protracted activation of a wound healing reaction leads to organ fibrosis. The phenotypic changes of activated HSCs involve epigenetic mechanisms mediated by non-coding RNAs (ncRNA) as well as by changes in DNA methylation and histone modifications. During CLD these epigenetic mechanisms become deregulated, with alterations in the expression and activity of epigenetic modulators. Here we provide an overview of the epigenetic alterations involved in fibrogenic HSCs transdifferentiation with particular focus on histones acetylation changes. We also discuss recent studies supporting the promising therapeutic potential of histone deacetylase inhibitors in liver fibrosis.https://www.mdpi.com/2073-4409/9/10/2321liver fibrosisepigeneticshistone deacetylasesprecision medicine |
| spellingShingle | Alex Claveria-Cabello Leticia Colyn Maria Arechederra Jesus M. Urman Carmen Berasain Matias A. Avila Maite G. Fernandez-Barrena Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target? Cells liver fibrosis epigenetics histone deacetylases precision medicine |
| title | Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target? |
| title_full | Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target? |
| title_fullStr | Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target? |
| title_full_unstemmed | Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target? |
| title_short | Epigenetics in Liver Fibrosis: Could HDACs be a Therapeutic Target? |
| title_sort | epigenetics in liver fibrosis could hdacs be a therapeutic target |
| topic | liver fibrosis epigenetics histone deacetylases precision medicine |
| url | https://www.mdpi.com/2073-4409/9/10/2321 |
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