ArticleMolecular endocrinology (Baltimore, Md.)2016
Glucocorticoids Have Opposing Effects on Liver Fibrosis in Hepatic Stellate and Immune Cells.
Article in Molecular endocrinology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Nanomedicine-Driven Modulation of Signaling Pathways in Hepatic Fibrosis.International journal of nanomedicine · 2026Review
- Superior Antiproliferative and Enhanced Synergistic Effects of a ROCK Inhibitor in Multiple Models for Keloid Disease.JID innovations : skin science from molecules to population health · 2025Article
- A meta-analysis of the efficacy and safety of immunomodulators in the treatment of severe COVID-19.The Journal of international medical research · 2025Article
- Impact of metabolic dysfunction-associated steatotic liver disease on hepatocellular carcinoma risk in autoimmune hepatitis.PloS one · 2025Article
- Normoglycemia and physiological cortisone level maintain glucose homeostasis in a pancreas-liver microphysiological system.Communications biology · 2024Article
- Article
- Article
- Development of novel liver-targeting glucocorticoid prodrugs.Medicine in drug discovery · 2024Article
- Concentration Effects of Methylprednisolone in Human Vocal Fold Fibroblast-Macrophage Co-Culture.The Laryngoscope · 2023Article
- Dose-Dependent Glucocorticoid Regulation of Transcription Factors in Vocal Fold Fibroblasts and Macrophages.The Laryngoscope · 2023Article
- Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.Journal of xenobiotics · 2022Review
- Prednisolone and mesenchymal stem cell preloading protect liver cell migration and mitigate extracellular matrix modification in transplanted decellularized rat liver.Stem cell research & therapy · 2022Article
- The role of immunosuppression in long-term graft hepatitis and fibrosis after paediatric liver transplant - comparison of two treatment protocols.Frontiers in transplantation · 2022Article
- Review
- Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment.Cell death & disease · 2021Article
- Glucocorticoids as Regulators of Macrophage-Mediated Tissue Homeostasis.Frontiers in immunology · 2021Review
- Steroids as rescue therapy for vitamin A-induced acute liver failure.BMJ case reports · 2020Article
- Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice.Frontiers in endocrinology · 2020Article
- Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Antibody-Directed Glucocorticoid Targeting to CD163 in M2-type Macrophages Attenuates Fructose-Induced Liver Inflammatory Changes.Molecular therapy. Methods & clinical development · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid receptor (GR), acting in immune cells and HSCs, in liver fibrosis. In the carbon tetrachloride hepatotoxin-induced fibrosis model, both steroidal and nonsteroidal GR ligands suppressed expression of fibrotic genes and decreased extracellular matrix deposition but also inhibited immune cell infiltration and exacerbated liver injury. These counteracting effects of GR ligands were dissociated in mice with conditional GR knockout in immune cells (GR(LysM)) or HSC (GR(hGFAP)): the impacts of dexamethasone on immune cell infiltration and liver injury were totally blunted in GR(LysM) mice, whereas the suppression of fibrotic gene expression was diminished in GR(hGFAP) mice. The effect of GR activation in HSC was further confirmed in the LX-2 HSC cell line, in which antifibrotic effects were mediated by GR ligand inhibition of Sma and mad-related protein 3 (SMAD3) expression. We conclude that GR has differential roles in immune cells and HSCs to modulate liver injury and liver fibrosis. Specific activation of HSC-GR without alteration of GR activity in immune cells provides a potential therapeutic approach to treatment of hepatic fibrosis.
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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.