ArticleScientific reports2015
Lessons from hepatocyte-specific Cyp51 knockout mice: impaired cholesterol synthesis leads to oval cell-driven liver injury.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Longevity-driven hepatic transcriptional programs mediate resilience to diet-induced liver injury in Ames dwarf mice.GeroScience · 2026Article
- Hepatic management of toxic sterols after acute deletion of Cyp51 from cholesterol synthesis.The Journal of biological chemistry · 2026Article
- Cross-Species Upregulation ofCurrent issues in molecular biology · 2026Article
- CYP51A1 in health and disease: from sterol metabolism to regulated cell death.Cell death discovery · 2025Review
- Deciphering the cell type-specific and zonal distribution of drug-metabolizing enzymes, transporters, and transcription factors in livers of mice using single-cell transcriptomics.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Knockouts ofiScience · 2024Article
- Mechanisms of pathogenicity and the quest for genetic modifiers of kidney disease in branchiootorenal syndrome.Clinical kidney journal · 2024Article
- Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures.Metabolites · 2023Review
- The expression pattern, subcellular localization and function of three sterol 14α-demethylases inFrontiers in genetics · 2023Article
- Cholesterol, lipoproteins, and COVID-19: Basic concepts and clinical applications.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
- Common Transcriptional Program of Liver Fibrosis in Mouse Genetic Models and Humans.International journal of molecular sciences · 2021Article
- Guided extraction of genome-scale metabolic models for the integration and analysis of omics data.Computational and structural biotechnology journal · 2021Article
- Chronic Disruption of the Late Cholesterol Synthesis Leads to Female-Prevalent Liver Cancer.Cancers · 2020Article
- Network and Systems Medicine: Position Paper of the European Collaboration on Science and Technology Action on Open Multiscale Systems Medicine.Network and systems medicine · 2020Review
- Article
- Differential lactate and cholesterol synthetic activities in XY and XX Sertoli cells.Scientific reports · 2017Article
- Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract.Human genetics · 2017Article
- Disrupting Hepatocyte Cyp51 from Cholesterol Synthesis Leads to Progressive Liver Injury in the Developing Mouse and Decreases RORC Signalling.Scientific reports · 2017Article
- Evaluation of Selected CYP51A1 Polymorphisms in View of Interactions with Substrate and Redox Partner.Frontiers in pharmacology · 2017Article
- Critical Role of Hepatic Cyp450s in the Testis-Specific Toxicity of (5R)-5-Hydroxytriptolide in C57BL/6 Mice.Frontiers in pharmacology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We demonstrate unequivocally that defective cholesterol synthesis is an independent determinant of liver inflammation and fibrosis. We prepared a mouse hepatocyte-specific knockout (LKO) of lanosterol 14α-demethylase (CYP51) from the part of cholesterol synthesis that is already committed to cholesterol. LKO mice developed hepatomegaly with oval cell proliferation, fibrosis and inflammation, but without steatosis. The key trigger was reduced cholesterol esters that provoked cell cycle arrest, senescence-associated secretory phenotype and ultimately the oval cell response, while elevated CYP51 substrates promoted the integrated stress response. In spite of the oval cell-driven fibrosis being histologically similar in both sexes, data indicates a female-biased down-regulation of primary metabolism pathways and a stronger immune response in males. Liver injury was ameliorated by dietary fats predominantly in females, whereas dietary cholesterol rectified fibrosis in both sexes. Our data place defective cholesterol synthesis as a focus of sex-dependent liver pathologies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.