Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension
Summary: Persistent liver injury triggers a fibrogenic program that causes pathologic remodeling of the hepatic microenvironment (i.e., liver fibrosis) and portal hypertension. The dynamics of gene regulation during liver disease progression and early regression remain understudied. Here, we generat...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224005224 |
| _version_ | 1797272426961174528 |
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| author | Oleksandr Petrenko Philipp Königshofer Ksenia Brusilovskaya Benedikt S. Hofer Katharina Bareiner Benedikt Simbrunner Frank Jühling Thomas F. Baumert Joachim Lupberger Michael Trauner Stefan G. Kauschke Larissa Pfisterer Eric Simon André F. Rendeiro Laura P.M.H. de Rooij Philipp Schwabl Thomas Reiberger |
| author_facet | Oleksandr Petrenko Philipp Königshofer Ksenia Brusilovskaya Benedikt S. Hofer Katharina Bareiner Benedikt Simbrunner Frank Jühling Thomas F. Baumert Joachim Lupberger Michael Trauner Stefan G. Kauschke Larissa Pfisterer Eric Simon André F. Rendeiro Laura P.M.H. de Rooij Philipp Schwabl Thomas Reiberger |
| author_sort | Oleksandr Petrenko |
| collection | DOAJ |
| description | Summary: Persistent liver injury triggers a fibrogenic program that causes pathologic remodeling of the hepatic microenvironment (i.e., liver fibrosis) and portal hypertension. The dynamics of gene regulation during liver disease progression and early regression remain understudied. Here, we generated hepatic transcriptome profiles in two well-established liver disease models at peak fibrosis and during spontaneous regression after the removal of the inducing agents. We linked the dynamics of key disease readouts, such as portal pressure, collagen area, and transaminase levels, to differentially expressed genes, enabling the identification of transcriptomic signatures of progressive vs. regressive liver fibrosis and portal hypertension. These candidate biomarkers (e.g., Tcf4, Mmp7, Trem2, Spp1, Scube1, Islr) were validated in RNA sequencing datasets of patients with cirrhosis and portal hypertension, and those cured from hepatitis C infection. Finally, deconvolution identified major cell types and suggested an association of macrophage and portal hepatocyte signatures with portal hypertension and fibrosis area. |
| first_indexed | 2024-03-07T14:28:08Z |
| format | Article |
| id | doaj.art-86925cb6106c40e38d57b9872bca512c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-07T14:28:08Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-86925cb6106c40e38d57b9872bca512c2024-03-06T05:28:33ZengElsevieriScience2589-00422024-03-01273109301Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertensionOleksandr Petrenko0Philipp Königshofer1Ksenia Brusilovskaya2Benedikt S. Hofer3Katharina Bareiner4Benedikt Simbrunner5Frank Jühling6Thomas F. Baumert7Joachim Lupberger8Michael Trauner9Stefan G. Kauschke10Larissa Pfisterer11Eric Simon12André F. Rendeiro13Laura P.M.H. de Rooij14Philipp Schwabl15Thomas Reiberger16Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna 1090, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna 1090, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna 1090, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna 1090, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna 1090, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna 1090, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna 1090, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna 1090, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna 1090, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna 1090, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna 1090, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hepatiques UMR_S1110, Strasbourg 67000, FranceUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hepatiques UMR_S1110, Strasbourg 67000, France; Service d’hépato-gastroentérologie, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France; Institut Universitaire de France (IUF), 75005 Paris, FranceUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hepatiques UMR_S1110, Strasbourg 67000, France; Service d’hépato-gastroentérologie, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France; Institut Universitaire de France (IUF), 75005 Paris, FranceDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna 1090, AustriaDepartment of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co.KG, 88397 Biberach an der Riss, GermanyDepartment of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co.KG, 88397 Biberach an der Riss, GermanyGlobal Computational Biology and Digital Sciences, Boehringer Ingelheim Pharma GmbH & Co.KG, 88397 Biberach an der Riss, GermanyCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna 1090, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna 1090, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna 1090, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna 1090, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, Austria; Corresponding authorSummary: Persistent liver injury triggers a fibrogenic program that causes pathologic remodeling of the hepatic microenvironment (i.e., liver fibrosis) and portal hypertension. The dynamics of gene regulation during liver disease progression and early regression remain understudied. Here, we generated hepatic transcriptome profiles in two well-established liver disease models at peak fibrosis and during spontaneous regression after the removal of the inducing agents. We linked the dynamics of key disease readouts, such as portal pressure, collagen area, and transaminase levels, to differentially expressed genes, enabling the identification of transcriptomic signatures of progressive vs. regressive liver fibrosis and portal hypertension. These candidate biomarkers (e.g., Tcf4, Mmp7, Trem2, Spp1, Scube1, Islr) were validated in RNA sequencing datasets of patients with cirrhosis and portal hypertension, and those cured from hepatitis C infection. Finally, deconvolution identified major cell types and suggested an association of macrophage and portal hepatocyte signatures with portal hypertension and fibrosis area.http://www.sciencedirect.com/science/article/pii/S2589004224005224DiseaseFibrosisIntegrative aspects of cell biologyModel organismTranscriptomics |
| spellingShingle | Oleksandr Petrenko Philipp Königshofer Ksenia Brusilovskaya Benedikt S. Hofer Katharina Bareiner Benedikt Simbrunner Frank Jühling Thomas F. Baumert Joachim Lupberger Michael Trauner Stefan G. Kauschke Larissa Pfisterer Eric Simon André F. Rendeiro Laura P.M.H. de Rooij Philipp Schwabl Thomas Reiberger Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension iScience Disease Fibrosis Integrative aspects of cell biology Model organism Transcriptomics |
| title | Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension |
| title_full | Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension |
| title_fullStr | Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension |
| title_full_unstemmed | Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension |
| title_short | Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension |
| title_sort | transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension |
| topic | Disease Fibrosis Integrative aspects of cell biology Model organism Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224005224 |
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