ArticleCellular and molecular gastroenterology and hepatology2018
Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model.
Article in Cellular and molecular gastroenterology and hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- The Non-Canonical ChREBPα Activity Suppresses the Activation of Hepatic Stellate Cells and Liver Fibrosis by Antagonizing TGF-β-E2F1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prognostic Value of the TLM3 Biomarker Panel for Early Fibrosis Development in MASLD Within the General Population.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Fibrogenic Gene Signature as Early Prediction for the Efficacy of Pharmacological Interventions for MASH-Associated Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Purinergic signaling in liver disease: calcium signaling and induction of inflammation.Purinergic signalling · 2025Review
- Therapeutic effects of FGF21 mimetic bFKB1 on MASH and atherosclerosis in Ldlr-/-.Leiden mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- miR-33 deletion in hepatocytes attenuates MASLD-MASH-HCC progression.JCI insight · 2024Article
- Development of a novel non-invasive biomarker panel for hepatic fibrosis in MASLD.Nature communications · 2024Article
- Evolutive Models, Algorithms and Predictive Parameters for the Progression of Hepatic Steatosis.Metabolites · 2024Article
- Integrating text mining with network models for successful target identification:Frontiers in pharmacology · 2024Article
- Acyl-CoA Thioesterase 1 Contributes to Transition of Steatosis to Metabolic-Associated Steatohepatitis.International journal of hepatology · 2024Article
- Found in translation-Fibrosis in metabolic dysfunction-associated steatohepatitis (MASH).Science translational medicine · 2023Review
- GepLiver: an integrative liver expression atlas spanning developmental stages and liver disease phases.Scientific data · 2023Article
- Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice.International journal of molecular sciences · 2023Article
- ANGPTL8 accelerates liver fibrosis mediated by HFD-induced inflammatory activity via LILRB2/ERK signaling pathways.Journal of advanced research · 2023Article
- The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr-/-.Leiden Mice.Nutrients · 2023Article
- Article
- Therapeutic Intervention with Anti-Complement Component 5 Antibody Does Not Reduce NASH but Does Attenuate Atherosclerosis and MIF Concentrations in Ldlr-/-.Leiden Mice.International journal of molecular sciences · 2022Article
- The potential of mecciRNA in hepatic stellate cell to regulate progression of nonalcoholic hepatitis.Journal of translational medicine · 2022Article
- Intervention with isoleucine or valine corrects hyperinsulinemia and reduces intrahepatic diacylglycerols, liver steatosis, and inflammation in Ldlr-/-.Leiden mice with manifest obesity-associated NASH.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThe incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis.
methodsA time-course study in low-density lipoprotein-receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis. An integrative systems biology approach was used to elucidate candidate markers linked to the active fibrosis process by combining transcriptomics, dynamic proteomics, and histopathology. The translational value of these findings were confirmed using human NASH data sets.
resultsHigh-fat-diet feeding resulted in obesity, hyperlipidemia, insulin resistance, and NASH with fibrosis in a time-dependent manner. Temporal dynamics of key molecular processes involved in the development of NASH were identified, including lipid metabolism, inflammation, oxidative stress, and fibrosis. A data-integrative approach enabled identification of the active fibrotic process preceding histopathologic detection using a novel molecular fibrosis signature. Human studies were used to identify overlap of genes and processes and to perform a network biology-based prioritization to rank top candidate markers representing the early manifestation of fibrosis.
conclusionsAn early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (pre)clinical experimental time frames.
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