ArticleGut2019
Glial cell line-derived neurotrophic factor (GDNF) mediates hepatic stellate cell activation via ALK5/Smad signalling.
Article in Gut, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- The post-transcriptional regulatory RNA-binding protein PTBP1 functions as an inhibitor in hepatic stellate cell activation and liver fibrosis.Molecular medicine (Cambridge, Mass.) · 2026Article
- Causal Relationship Between Neurotrophins and Normal Pressure Hydrocephalus: Insights From a Bidirectional Two-Sample Mendelian Randomization Study.Brain and behavior · 2026Article
- Aspartate treatment ameliorates metabolic dysfunction-associated fatty liver disease through upregulation of CBS and suppression of ferroptosis.The Journal of biological chemistry · 2026Article
- Prevalence of non-HLA antibodies and their association with FIB-4 index-based fibrosis risk in pediatric liver transplant recipients with long-term graft survival (>10 years).Frontiers in immunology · 2026Article
- MertkImmunity, inflammation and disease · 2025Article
- Inhibition of GDNF-Driven Macrophage-to-Myofibroblast Transition Protects Against Colitis-Associated Intestinal Fibrosis.Inflammation · 2025Article
- Anti-integrin αvβ6 Autoantibodies Are Increased in Primary Sclerosing Cholangitis Patients With Concomitant Inflammatory Bowel Disease and Correlate With Liver Disease Severity.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2025Article
- In Situ Assembly of Fluorogenic RNA for Screening Natural Anti-Liver Fibrosis Products via Dynamic Visualization of COL1A1 mRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting neurotrophic dysregulation in diabetic retinopathy: a novel therapeutic avenue.Molecular biology reports · 2025Review
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- SARM1 in the pathogenesis of immune-related disease.Toxicology research · 2024Review
- Glial-Cell-Line-Derived Neurotrophic Factor Promotes Glioblastoma Cell Migration and Invasion via the SMAD2/3-SERPINE1-Signaling Axis.International journal of molecular sciences · 2024Article
- MicroRNA-Mediated Suppression of Glial Cell Line-Derived Neurotrophic Factor Expression Is Modulated by a Schizophrenia-Associated Non-Coding Polymorphism.International journal of molecular sciences · 2024Article
- Hepatocyte-derived exosomes deliver the lncRNA CYTOR to hepatic stellate cells and promote liver fibrosis.Journal of cellular and molecular medicine · 2024Article
- Utilization of the Rat Tibial Nerve Transection Model to Evaluate Cellular and Molecular Mechanisms Underpinning Denervation-Mediated Muscle Injury.International journal of molecular sciences · 2024Article
- Treatment of Obesity Through Glial Cell-Derived Neurotrophic Factor Lipid Nanoparticle Delivery in Mice.Gastro hep advances · 2024Article
- Review
- An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease.Nature medicine · 2023Article
- Overview of CircRNAs Roles and Mechanisms in Liver Fibrosis.Biomolecules · 2023Review
- CRISPR/dCas9 for hepatic fibrosis therapy: implications and challenges.Molecular biology reports · 2022Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveAlthough glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-β superfamily, its function in liver fibrosis has rarely been studied. Here, we investigated the role of GDNF in hepatic stellate cell (HSC) activation and liver fibrosis in humans and mice.
designGDNF expression was examined in liver biopsies and sera from patients with liver fibrosis. The functional role of GDNF in liver fibrosis was examined in mice with adenoviral delivery of the GDNF gene, GDNF sgRNA CRISPR/Cas9 and the administration of GDNF-blocking antibodies. GDNF was examined on HSC activation using human and mouse primary HSCs. The binding of activin receptor-like kinase 5 (ALK5) to GDNF was determined using surface plasmon resonance (SPR), molecular docking, mutagenesis and co-immunoprecipitation.
resultsGDNF mRNA and protein levels are significantly upregulated in patients with stage F4 fibrosis. Serum GDNF content correlates positively with α-smooth muscle actin (α-SMA) and Col1A1 mRNA in human fibrotic livers. Mice with overexpressed GDNF display aggravated liver fibrosis, while mice with silenced GDNF expression or signalling inhibition by GDNF-blocking antibodies have reduced fibrosis and HSC activation. GDNF is confined mainly to HSCs and contributes to HSC activation through ALK5 at His
conclusionsGDNF promotes HSC activation and liver fibrosis through ALK5/Smad signalling. Inhibition of GDNF could be a novel therapeutic strategy to combat liver 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.