ArticlePloS one2012
Inhibition of glycogen synthase kinase 3β ameliorates D-GalN/LPS-induced liver injury by reducing endoplasmic reticulum stress-triggered apoptosis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Selective PPARδ Agonist GW501516 Protects Against LPS-Induced Macrophage Inflammation and Acute Liver Failure in Mice via Suppressing Inflammatory Mediators.Molecules (Basel, Switzerland) · 2024Article
- Interleukin-1β Signaling Contributes to Cell Cycle Arrest and Apoptotic Cell Death by Leptin via Modulation of AKT and p38MAPK in Hepatocytes.Biomolecules & therapeutics · 2024Article
- Nebivolol protects the liver against lipopolysaccharide-induced oxidative stress, inflammation, and endoplasmic reticulum-related apoptosis through Chop and Bip/GRP78 signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- GSK3-Driven Modulation of Inflammation and Tissue Integrity in the Animal Model.International journal of molecular sciences · 2024Review
- Cilostazol Combats Lipopolysaccharide-Induced Hippocampal Injury in Rats: Role of AKT/GSK3Advances in pharmacological and pharmaceutical sciences · 2024Article
- TDAG51 promotes transcription factor FoxO1 activity during LPS-induced inflammatory responses.The EMBO journal · 2023Article
- Article
- Article
- Role of Glycogen Synthase Kinase-3 in Interferon-γ-Mediated Immune Hepatitis.International journal of molecular sciences · 2022Review
- Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.Medicinal research reviews · 2022Review
- Changes in Mitochondria-Related Gene Expression upon Acupuncture at LR3 in the D-Galactosamine-Induced Liver Damage Rat Model.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Article
- miR-29a Modulates GSK3β/SIRT1-Linked Mitochondrial Proteostatic Stress to Ameliorate Mouse Non-Alcoholic Steatohepatitis.International journal of molecular sciences · 2020Article
- Exacerbated LPS/GalN-Induced Liver Injury in the Stress-Sensitive Wistar Kyoto Rat Is Associated with Changes in the Endocannabinoid System.Molecules (Basel, Switzerland) · 2020Article
- Hepatic Inflammatory Response to Exogenous LPS Challenge is Exacerbated in Broilers with Fatty Liver Disease.Animals : an open access journal from MDPI · 2020Article
- Tender coconut water suppresses hepatic inflammation by activating AKT and JNK signaling pathways in anJournal of functional foods · 2020Article
- TAK242 suppresses the TLR4 signaling pathway and ameliorates DCD liver IRI in rats.Molecular medicine reports · 2019Article
- Valproate reduces neuroinflammation and neuronal death in a rat chronic constriction injury model.Scientific reports · 2018Article
- Anti‑apoptotic effects of human placental hydrolysate against hepatocyte toxicity in vivo and in vitro.International journal of molecular medicine · 2018Article
- [Interaction between glycogen synthase kinase-3β and endoplasmic reticulum stress is involved in high glucose-induced injury in human umbilical vein endothelial cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlycogen synthase kinase 3β(GSK3β) is a ubiquitous serine-threonine protein kinase that participates in numerous cellular processes and disease pathophysiology. We aimed to determine therapeutic potential of GSK3β inhibition and its mechanism in a well-characterized model of lipopolysaccharide (LPS)-induced model of acute liver failure (ALF). METHODOLOGY: In a murine ALF model induced by D-GalN(700 mg/kg)/LPS(10 µg/kg), we analyzed GSK3β mechanisms using a specific chemical inhibitor, SB216763, and detected the role of endoplasmic reticulum stress (ERS). Mice were administered SB216763 at 2 h before or after D-GalN/LPS injection, respectively, and then sacrificed 6 h after D-GalN/LPS treatment to evaluate its prophylactic and therapeutic function. The lethality rate, liver damage, ERS, cytokine expression, MAP kinase, hepatocyte apoptosis and expression of TLR 4 were evaluated, respectively. Whether the inhibition of GSK3β activation protected hepatocyte from ERS-induced apoptosis was investigated in vitro. PRINCIPAL
findingsGSK3β became quickly activated (dephosphorylated) upon D-GalN/LPS exposure. Administration of SB216763 not only ameliorated liver injury, as evidenced by reduced transaminase levels, and well-preserved liver architecture, but also decreased lethality. Moreover, GSK3β inhibition resulted in down-regulation of pro-apoptotic proteins C/EBP-homologous protein(CHOP) and caspase-12, which are related to ERS. To further demonstrate the role of ERS, we found that GSK3β inhibition protected hepatocyte from ERS-induced cell death. GSK3β inhibition down-regulated the MAPK pathways, reduced expression of inflammatory cytokines and decreased expression of TLR4.
conclusionsOur findings demonstrate the key function of GSK3β signaling in the pathophysiology of ALF, especially in regulating the ERS, and provide a rationale for targeting GSK3β as a potential therapeutic strategy to ameliorate ALF.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.