ArticleLiver international : official journal of the International Association for the Study of the Liver2010
Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia-inducible factor and transforming growth factor-beta-dependent mechanisms.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
94 citing papers in PubMed, 165 citations in OpenAlex.
- Hepatic stellate cells in alcoholic liver cirrhosis: mechanisms of fibrogenesis, plasticity, and fibrosis reversal.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Advances in In Vitro Vascularization of Engineered Tissues: From Microvessel Formation to Hepatic Tissue Integration.Regenerative therapy · 2026Article
- The role of naturally-occurring canine tumors in translating conserved consequences of epithelial-mesenchymal plasticity to human cancers.Frontiers in veterinary science · 2026Review
- Breaking hypoxic barrier: Oxygen-supplied nanomaterials for enhanced T cell-mediated tumor immunotherapy.International journal of pharmaceutics: X · 2025Review
- Transforming Cancer Therapy: Unlocking the Potential of Targeting Vascular and Stromal Cells in the Tumor Microenvironment.Cancer research · 2025Review
- COVID-19 Induces Greater NLRP3 Inflammasome Activation in Obese Patients than Other Chronic Illnesses: A Case-Control Study.International journal of molecular sciences · 2025Article
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- Revisiting Treatment Strategies: Addressing Epithelial-to-Mesenchymal Transition-Induced Resistance in Hepatocellular Carcinoma.BME frontiers · 2025Review
- Oxidative Stress and Cancer Therapy: Controlling Cancer Cells Using Reactive Oxygen Species.International journal of molecular sciences · 2024Review
- Protective Effects of Anethole inAntioxidants (Basel, Switzerland) · 2024Article
- Fibrosis and Hepatocarcinogenesis: Role of Gene-Environment Interactions in Liver Disease Progression.International journal of molecular sciences · 2024Review
- Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders: from molecular mechanisms to clinical implications.Medical review (2021) · 2024Review
- Forces at play: exploring factors affecting the cancer metastasis.Frontiers in immunology · 2024Review
- An Overview of Epithelial-to-Mesenchymal Transition and Mesenchymal-to-Epithelial Transition in Canine Tumors: How Far Have We Come?Veterinary sciences · 2022Review
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Bone marrow mesenchymal stem cells facilitate diabetic wound healing through the restoration of epidermal cell autophagy via the HIF-1α/TGF-β1/SMAD pathway.Stem cell research & therapy · 2022Article
- Review
- Exosomes as a messager to regulate the crosstalk between macrophages and cardiomyocytes under hypoxia conditions.Journal of cellular and molecular medicine · 2022Article
- Intraperitoneal Triamcinolone Reduces Postoperative Adhesions, Possibly through Alteration of Mitochondrial Function.Journal of clinical medicine · 2022Article
- Association of the TGFβ gene family with microenvironmental features of gastric cancer and prediction of response to immunotherapy.Frontiers in oncology · 2022Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
BACKGROUND/
aimsDuring development of liver fibrosis, an important source of myofibroblasts is hepatocytes, which differentiate into myofibroblasts by epithelial to mesenchymal transition (EMT). In epithelial tumours and kidney fibrosis, hypoxia, through activation of hypoxia-inducible factors (HIFs), is an important stimulus of EMT. Our recent studies demonstrated that HIF-1alpha is important for the development of liver fibrosis. Accordingly, the hypothesis was tested that hypoxia stimulates hepatocyte EMT by a HIF-dependent mechanism.
methodsPrimary mouse hepatocytes were exposed to room air or 1% oxygen and EMT evaluated. In addition, bile duct ligations (BDLs) were performed in control and HIF-1alpha-deficient mice and EMT quantified.
resultsExposure of hepatocytes to 1% oxygen increased expression of alpha-smooth muscle actin, vimentin, Snail and fibroblast-specific protein-1 (FSP-1). Levels of E-cadherin and zona occludens-1 were decreased. Upregulation of FSP-1 and Snail by hypoxia was completely prevented in HIF-1beta-deficient hepatocytes and by pretreatment with SB431542, a transforming growth factor-beta (TGF-beta) receptor inhibitor. HIFs promoted TGF-beta-dependent EMT by stimulating activation of latent TGF-beta1. To determine whether HIF-1alpha contributes to EMT in the liver during the development of fibrosis, control and HIF-1alpha-deficient mice were subjected to BDL. FSP-1 was increased to a greater extent in the livers of control mice when compared with HIF-1alpha-deficient mice.
conclusionsResults from these studies demonstrate that hypoxia stimulates hepatocyte EMT by a HIF and TGF-beta-dependent mechanism. Furthermore, these studies suggest that HIF-1alpha is important for EMT in the liver during the development of fibrosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.