ArticleJournal of hepatology2014
Gli1 activation and protection against hepatic encephalopathy is suppressed by circulating transforming growth factor β1 in mice.
Article in Journal of hepatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 29 citations in OpenAlex.
- Mechanisms of Huangqi Decoction Granules () on Hepatitis B Cirrhosis Patients Based on RNA-Sequencing.Chinese journal of integrative medicine · 2019Trial
- Systemic TGF-β1 reduction contributes to neuronal GLUT4 trafficking impairment in acute hepatic encephalopathy.Frontiers in molecular neuroscience · 2026Article
- Ataxia-telangiectasia mutated activation mediates transforming growth factor beta signaling in acetaminophen-induced liver injury in mice.Physiological reports · 2025Article
- The gut-brain axis underlying hepatic encephalopathy in liver cirrhosis.Nature medicine · 2025Article
- Gut Dysbiosis and Blood-Brain Barrier Alteration in Hepatic Encephalopathy: From Gut to Brain.Biomedicines · 2023Review
- The multifaceted role of macrophages during acute liver injury.Frontiers in immunology · 2023Review
- The Effect of TGF-β1 Reduced Functionality on the Expression of Selected Synaptic Proteins and Electrophysiological Parameters: Implications of Changes Observed in Acute Hepatic Encephalopathy.International journal of molecular sciences · 2022Article
- Hepatic TGFβr1 Deficiency Attenuates Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure Through Inhibiting GSK3β-Nrf2-Mediated Hepatocyte Apoptosis and Ferroptosis.Cellular and molecular gastroenterology and hepatology · 2022Article
- 2021 ISHEN guidelines on animal models of hepatic encephalopathy.Liver international : official journal of the International Association for the Study of the Liver · 2021Review
- Article
- Thrombospondin-1 Exacerbates Acute Liver Failure and Hepatic Encephalopathy Pathology in Mice by Activating Transforming Growth Factor β1.The American journal of pathology · 2020Article
- Protective Effects of Flavone fromInternational journal of molecular sciences · 2019Article
- The TGFβ1 Receptor Antagonist GW788388 Reduces JNK Activation and Protects Against Acetaminophen Hepatotoxicity in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Elevated circulating TGFβ1 during acute liver failure activates TGFβR2 on cortical neurons and exacerbates neuroinflammation and hepatic encephalopathy in mice.Journal of neuroinflammation · 2019Article
- TGF-β2 Induces Gli1 in a Smad3-Dependent Manner Against Cerebral Ischemia/Reperfusion Injury After Isoflurane Post-conditioning in Rats.Frontiers in neuroscience · 2019Article
- Direct Comparison of the Thioacetamide and Azoxymethane Models of Type A Hepatic Encephalopathy in Mice.Gene expression · 2018Article
- Cortical Synaptic Transmission and Plasticity in Acute Liver Failure Are Decreased by Presynaptic Events.Molecular neurobiology · 2018Article
- FXR-Mediated Cortical Cholesterol Accumulation Contributes to the Pathogenesis of Type A Hepatic Encephalopathy.Cellular and molecular gastroenterology and hepatology · 2018Article
- Bile Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Promotes Neuroinflammation during Hepatic Encephalopathy in Mice.Frontiers in cellular neuroscience · 2017Article
- Recent advances in hepatic encephalopathy.F1000Research · 2017Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsHepatic encephalopathy (HE) is a neurologic disorder that develops during liver failure. Few studies exist investigating systemic-central signalling during HE outside of inflammatory signalling. The transcription factor Gli1, which can be modulated by hedgehog signalling or transforming growth factor β1 (TGFβ1) signalling, has been shown to be protective in various neuropathies. We measured Gli1 expression in brain tissues from mice and evaluated how circulating TGFβ1 and canonical hedgehog signalling regulate its activation.
methodsMice were injected with azoxymethane (AOM) to induce liver failure and HE in the presence of Gli1 vivo-morpholinos, the hedgehog inhibitor cyclopamine, Smoothened vivo-morpholinos, a Smoothened agonist, or TGFβ-neutralizing antibodies. Molecular analyses were used to assess Gli1, hedgehog signalling, and TGFβ1 signalling in the liver and brain of AOM mice and HE patients.
resultsGli1 expression was increased in brains of AOM mice and in HE patients. Intra-cortical infusion of Gli1 vivo-morpholinos exacerbated the neurologic deficits of AOM mice. Measures to modulate hedgehog signalling had no effect on HE neurological decline. Levels of TGFβ1 increased in the liver and serum of mice following AOM administration. TGFβ neutralizing antibodies slowed neurologic decline following AOM administration without significantly affecting liver damage. TGFβ1 inhibited Gli1 expression via a SMAD3-dependent mechanism. Conversely, inhibiting TGFβ1 increased Gli1 expression.
conclusionsCortical activation of Gli1 protects mice from induction of HE. TGFβ1 suppresses Gli1 in neurons via SMAD3 and promotes the neurologic decline. Strategies to activate Gli1 or inhibit TGFβ1 signalling might be developed to treat patients with HE.
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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.