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Sökning: WFRF:(Rosso Chiara) > (2020) > Transcriptomic prof...

Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis

Govaere, Olivier (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Cockell, Simon (författare)
Bioinformatics Support Unit, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Tiniakos, Dina (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Department of Pathology, Aretaieio Hospital, National and Kapodistrian University of Athens, Athens, Greece,Newcastle Univ, England; Natl & Kapodistrian Univ Athens, Greece
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Queen, Rachel (författare)
Bioinformatics Support Unit, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Younes, Ramy (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy,Newcastle Univ, England; Univ Turin, Italy
Vacca, Michele (författare)
University of Cambridge Metabolic Research Laboratories, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK,Univ Cambridge, England
Alexander, Leigh (författare)
SomaLogic Inc., Boulder, CO, USA,SomaL Inc, CO 80301 USA
Ravaioli, Federico (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy,Newcastle Univ, England; Univ Bologna, Italy
Palmer, Jeremy (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Petta, Salvatore (författare)
Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy,Univ Palermo, Italy
Boursier, Jerome (författare)
Hepatology Department, Angers University Hospital, Angers, France,Angers Univ Hosp, France
Rosso, Chiara (författare)
Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy,Univ Turin, Italy
Johnson, Katherine (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Wonders, Kristy (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Day, Christopher P. (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Ekstedt, Mattias (författare)
Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken
Oresic, Matej, 1967- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Orebro Univ, Sweden
Darlay, Rebecca (författare)
Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Cordell, Heather J. (författare)
Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Marra, Fabio (författare)
Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy,Univ Florence, Italy
Vidal-Puig, Antonio (författare)
University of Cambridge Metabolic Research Laboratories, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK,Univ Cambridge, England
Bedossa, Pierre (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Assistance Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Sorbonne University, ICAN (Institute of Cardiometabolism and Nutrition), Paris, France,Newcastle Univ, England; Sorbonne Univ, France
Schattenberg, Jörn M. (författare)
Department of Medicine, University Hospital Mainz, Mainz, Germany,Univ Hosp Mainz, Germany
Clément, Karine (författare)
Nutrition and Obesities: Systemic Approaches, INSERM, Sorbonne University, Paris, France,Sorbonne Univ, France
Allison, Michael (författare)
Liver Unit, Department of Medicine, NIHR Cambridge Biomedical Research Centre, Cambridge University NHS Foundation Trust, Cambridge, UK,Cambridge Univ NHS Fdn Trust, England
Bugianesi, Elisabetta (författare)
Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy,Univ Turin, Italy
Ratziu, Vlad (författare)
Assistance Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Sorbonne University, ICAN (Institute of Cardiometabolism and Nutrition), Paris, France,Sorbonne Univ, France
Daly, Ann K. (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK,Newcastle Univ, England
Anstee, Quentin M. (författare)
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK,Newcastle Univ, England; Newcastle Tyne Hosp NHS Trust, England
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 (creator_code:org_t)
Washington, DC, United States : American Association for the Advancement of Science (AAAS), 2020
2020
Engelska.
Ingår i: Science Translational Medicine. - Washington, DC, United States : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 12:572
Relaterad länk:
https://eprints.ncl....
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https://urn.kb.se/re...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • The mechanisms that drive nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This large multicenter study characterized the transcriptional changes that occur in liver tissue across the NAFLD spectrum as disease progresses to cirrhosis to identify potential circulating markers. We performed high-throughput RNA sequencing on a discovery cohort comprising histologically characterized NAFLD samples from 206 patients. Unsupervised clustering stratified NAFLD on the basis of disease activity and fibrosis stage with differences in age, aspartate aminotransferase (AST), type 2 diabetes mellitus, and carriage of PNPLA3 rs738409, a genetic variant associated with NAFLD. Relative to early disease, we consistently identified 25 differentially expressed genes as fibrosing steatohepatitis progressed through stages F2 to F4. This 25-gene signature was independently validated by logistic modeling in a separate replication cohort (n = 175), and an integrative analysis with publicly available single-cell RNA sequencing data elucidated the likely relative contribution of specific intrahepatic cell populations. Translating these findings to the protein level, SomaScan analysis in more than 300 NAFLD serum samples confirmed that circulating concentrations of proteins AKR1B10 and GDF15 were strongly associated with disease activity and fibrosis stage. Supporting the biological plausibility of these data, in vitro functional studies determined that endoplasmic reticulum stress up-regulated expression of AKR1B10, GDF15, and PDGFA, whereas GDF15 supplementation tempered the inflammatory response in macrophages upon lipid loading and lipopolysaccharide stimulation. This study provides insights into the pathophysiology of progressive fibrosing steatohepatitis, and proof of principle that transcriptomic changes represent potentially tractable and clinically relevant markers of disease progression.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

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