ArticlePloS one2017
Both MAPK and STAT3 signal transduction pathways are necessary for IL-6-dependent hepatic stellate cells activation.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 92 citations in OpenAlex.
- Hepatic Overexpression of a Novel Soluble Endogenous Transforming Growth Factor β Type II Receptor-Immunoglobulin G1 Fc Fusion Protein (TβRII-SE/Fc) Attenuates Early Stage Metabolic Dysfunction-Associated Steatotic Liver Disease in Rats.ACS pharmacology & translational science · 2026Article
- Structural and Functional Characteristics of the Liver After Fractionated Local Electron Irradiation and Against the Background of Ascorbic Acid Administration.Journal of personalized medicine · 2026Review
- Article
- Macrophage regulation of extracellular matrix remodeling in aging skeletal muscle.Ageing research reviews · 2026Review
- Tet2 deficiency-induced expansion of monocyte-derived macrophages promotes liver fibrosis.The Journal of experimental medicine · 2026Article
- Plasma GLP-1 (Glucagon-like Peptide-1) Depletion Is Correlated with Dysregulation of Adipocytokine in Type 2 Diabetic Patients With or Without Metabolic-Associated Fatty Liver Disease (MAFLD): A Cross-Sectional Study Related to Gender-Sex Disparities.International journal of molecular sciences · 2026Article
- Exploring the Therapeutic Potential of TGF-β Inhibitors for Liver Fibrosis: Targeting Multiple Signaling Pathways.Journal of clinical and translational hepatology · 2025Review
- Empagliflozin reduces liver fibrosis by restoring catechol-O-methyltransferase activity associated with magnesium levels.Scientific reports · 2025Article
- AAV8-mediated silencing of Atad3 prevents the progression from simple steatosis to MASH in mice by reduced IL6 secretion.Biochimica et biophysica acta. Molecular basis of disease · 2025Article
- Casein kinase 1 epsilon (CK1ε) as a potential therapeutic target in chronic liver disease.Journal of veterinary science · 2025Review
- Carabrone Attenuates Metabolic Dysfunction-Associated Steatohepatitis by Targeting STAT3 in Mice.MedComm · 2025Article
- The role of the interleukin family in liver fibrosis.Frontiers in immunology · 2025Review
- Daratumumab monotherapy in a patient with kappa light chain multiple myeloma and decompensated cirrhosis: a case report.Frontiers in oncology · 2025Article
- Advancements in the understanding of mechanisms of the IL-6 family in relation to metabolic-associated fatty liver disease.Frontiers in endocrinology · 2025Review
- Anti-CLL1 liposome loaded with miR-497-5p and venetoclax as a novel therapeutic strategy in acute myeloid leukemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Interleukin receptor therapeutics attenuate inflammation in canine synovium following cruciate ligament injury.Osteoarthritis and cartilage · 2024Article
- Review
- A First Metabolite Analysis of Norfolk Island Pine Resin and Its Hepatoprotective Potential to Alleviate Methotrexate (MTX)-Induced Hepatic Injury.Pharmaceuticals (Basel, Switzerland) · 2024Article
- [Tofacitinib inhibits the transformation of lung fibroblasts into myofibroblasts through JAK/STAT3 pathway].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- LX-2 Stellate Cells Are a Model System for Investigating the Regulation of Hepatic Vitamin A Metabolism and Respond to Tumor Necrosis FactorDrug metabolism and disposition: the biological fate of chemicals · 2024Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDuring liver injury, hepatic stellate cells (HSCs) can undergo activation and transform into alpha-smooth muscle actin (αSMA)-expressing contractile myofibroblast-like cells, leading to deposition of excessive scar matrix. We have recently demonstrated that depletion of adenosine deaminase acting on double-stranded RNA (ADAR1) from mouse hepatocytes leads to HSC activation and induction of inflammation and hepatic fibrosis that is mediated by interleukin 6 (IL-6). Our aim was to identify and characterize the molecular pathways involved in the direct, inflammation-independent activation of HSCs by IL-6.
methodsPrimary HSCs were isolated from mouse livers. mRNA levels of αSMA and Col1a were analyzed using qRT-PCR. Protein levels of αSMA, MAPK, p-MAPK, p38, p-p38, STAT3 and p-STAT3 were assessed by Western Blot analysis. The effect of specific signal transduction pathway inhibitors (i.e., SB203580 (P-38 inhibitor), U0126 (MAPK inhibitor), S3I-201 (STAT3 inhibitor) and Ruxolitinib (Jak1/2 inhibitor)) was also studied.
resultsPrimary HSCs treated with IL-6 demonstrated upregulation of αSMA and Col1a mRNA levels as well as increased αSMA protein levels. Moreover, the phenotypic transition of quiescent HSCs toward myofibroblast-like cells was noted upon administration of IL-6 and not in untreated samples. In addition, the phosphorylation levels of p38, MAPK and STAT3 increased 30 minutes after treatment, and was followed by a decline in the phosphorylation levels 2-4 hours post-treatment. However, addition of specific signal transduction pathway inhibitors curbed this effect, and resulted in αSMA and Col1a expression levels similar to those measured in untreated control samples.
conclusionIL-6 can directly induce the transition of HSCs toward myofibroblast-like cells. The effect is mediated by the activation of both MAPK and JAK/STAT signaling pathways. Elimination of either MAPK or JAK/STAT signaling pathways inhibits HSC stimulation. These results might pave the road toward the development of potential therapeutic interventions for hepatic fibrosis.
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