ArticlePloS one2007
A ribosomal S-6 kinase-mediated signal to C/EBP-beta is critical for the development of liver fibrosis.
Article in PloS one, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05361733 (A Phase 1, Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of XFB19 in Healthy Adult Volunteers.), which is not on this map. Cited by 27 papers.
What it found
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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.
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.
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of XFB19 in Healthy Adult Volunteers.
Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Integrated WGCNA of lncRNA-mRNA Networks Identifies Novel Hub Genes and Potential Therapeutic Agents for Liver Cirrhosis via Molecular Docking Validation.International journal of molecular sciences · 2026Article
- TGFβ pathway represses hepatic ribosome biogenesis and protein synthesis by regulating p70S6K-S6RP proteins.Cellular & molecular biology letters · 2026Article
- Ribosome biogenesis: A central player in liver diseases.Genes & diseases · 2025Review
- RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.Expert opinion on therapeutic targets · 2024Review
- Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in Offspring.Cellular and molecular gastroenterology and hepatology · 2024Article
- Effect of distinct ECM microenvironments on the genome-wide chromatin accessibility and gene expression responses of hepatic stellate cells.Acta biomaterialia · 2023Article
- Immune cell C/EBPβ deficiency is associated with hepatic mononuclear defects and spontaneous hepatitis but not steatohepatitis induced liver fibrosis.Immunity, inflammation and disease · 2022Article
- CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding.Research (Washington, D.C.) · 2022Review
- Role of Granulocyte Colony-stimulating Factor Therapy in Cirrhosis, 'Inside Any Deep Asking Is the Answering'.Journal of clinical and translational hepatology · 2019Review
- The serum amyloid A3 promoter-driven luciferase reporter mice is a valuable tool to image early renal fibrosis development and shows the therapeutic effect of glucosyl-hesperidin treatment.Scientific reports · 2019Article
- Article
- C/EBPβ-Thr217 Phosphorylation Stimulates Macrophage Inflammasome Activation and Liver Injury.Scientific reports · 2016Article
- Liquiritigenin Protects Rats from Carbon Tetrachloride Induced Hepatic Injury through PGC-1α Pathway.Evidence-based complementary and alternative medicine : eCAM · 2015Article
- Extracellular matrix and liver disease.Antioxidants & redox signaling · 2014Review
- Mesenchymal-specific deletion of C/EBPβ suppresses pulmonary fibrosis.The American journal of pathology · 2012Article
- Expression2Kinases: mRNA profiling linked to multiple upstream regulatory layers.Bioinformatics (Oxford, England) · 2012Article
- Elevated activation of ERK1 and ERK2 accompany enhanced liver injury following alcohol binge in chronically ethanol-fed rats.Alcoholism, clinical and experimental research · 2011Article
- C/EBPβ-Thr217 phosphorylation signaling contributes to the development of lung injury and fibrosis in mice.PloS one · 2011Article
- Evolving challenges in hepatic fibrosis.Nature reviews. Gastroenterology & hepatology · 2010Review
- RSK2 Binding Models Delineate Key Features for Activity.Journal of chemical and pharmaceutical research · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn response to liver injury, hepatic stellate cell (HSC) activation causes excessive liver fibrosis. Here we show that activation of RSK and phosphorylation of C/EBPbeta on Thr217 in activated HSC is critical for the progression of liver fibrosis. METHODOLOGY/PRINCIPAL
findingsChronic treatment with the hepatotoxin CCl(4) induced severe liver fibrosis in C/EBPbeta(+/+) mice but not in mice expressing C/EBPbeta-Ala217, a non-phosphorylatable RSK-inhibitory transgene. C/EBPbeta-Ala217 was present within the death receptor complex II, with active caspase 8, and induced apoptosis of activated HSC. The C/EBPbeta-Ala217 peptides directly stimulated caspase 8 activation in a cell-free system. C/EBPbeta(+/+) mice with CCl(4)-induced severe liver fibrosis, while continuing on CCl(4), were treated with a cell permeant RSK-inhibitory peptide for 4 or 8 weeks. The peptide inhibited RSK activation, stimulating apoptosis of HSC, preventing progression and inducing regression of liver fibrosis. We found a similar activation of RSK and phosphorylation of human C/EBPbeta on Thr266 (human phosphoacceptor) in activated HSC in patients with severe liver fibrosis but not in normal livers, suggesting that this pathway may also be relevant in human liver fibrosis. CONCLUSIONS/SIGNIFICANCE: These data indicate that the RSK-C/EBPbeta phosphorylation pathway is critical for the development of liver fibrosis and suggest a potential therapeutic target.
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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.