ArticleJCI insight2020
ASK1 inhibition reduces cell death and hepatic fibrosis in an Nlrp3 mutant liver injury model.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 69 citations in OpenAlex.
- Plasma proteome signatures of ASK1 inhibition by selonsertib associate with efficacy in the MOSAIC randomized trial for diabetic kidney disease.BMC nephrology · 2025Trial
- Limited impact of NLRP3 inflammasome deficiency on diet-induced metabolic dysfunction-associated steatohepatitis in mice.Biochemistry and biophysics reports · 2026Article
- Contribution of p38 MAPK in liver fibrosis: An overview of mechanisms, signaling pathways, and therapeutic targets (Review).International journal of molecular medicine · 2026Review
- MASLD: Spatial Mechanisms and New Therapeutics.Biomolecules · 2026Review
- Deep Learning-Based Virtual Screening Identifies Potential Small-Molecule Inhibitors of ASK1: Natural Product Lead Discovery for MASH.International journal of molecular sciences · 2026Article
- DN203316, a novel PPARδ agonist, suppresses ferroptotic signaling and fibrogenesis in metabolic dysfunction-associated steatohepatitis.Experimental & molecular medicine · 2026Article
- Review
- Palmatine ameliorates MASLD in type 2 diabetes by modulating hepatic apoptosis and inflammation.Scientific reports · 2026Article
- Thioredoxin-Binding protein 2 and apoptosis Signal-Regulating kinase 1: redox stress sensors and therapeutic targets in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators.Beilstein journal of organic chemistry · 2026Article
- Updated insights on ASK1 signaling: mechanisms, regulation, and therapeutic potential in diseases.Molecular and cellular biochemistry · 2025Review
- Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2025Review
- HSC-derived exosomal miR-122-5p inhibits EMT and fibrosis of intrahepatic biliary epithelial cells to alleviate primary biliary cholangitis.Frontiers in immunology · 2025Article
- Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models.Animal models and experimental medicine · 2025Article
- Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Development of novel ALOX15 inhibitors combining dual machine learning filtering and fragment substitution optimisation approaches, molecular docking and dynamic simulation methods.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Synthesis and biological evaluation of quinoxaline derivatives as ASK1 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Inflammasomes in chronic liver disease: Hepatic injury, fibrosis progression and systemic inflammation.Journal of hepatology · 2024Review
- Honey vesicle-like nanoparticles protect aged liver from non-alcoholic steatohepatitis.Acta pharmaceutica Sinica. B · 2024Article
- Targeting chronic liver diseases: Molecular markers, drug delivery strategies and future perspectives.International journal of pharmaceutics · 2024Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatic inflammasome activation is considered a major contributor to liver fibrosis in NASH. Apoptosis signal-regulating kinase 1 (ASK1) is an apical mitogen-activated protein kinase that activates hepatic JNK and p38 to promote apoptosis, inflammation, and fibrosis. The aim of the current study was to investigate whether pharmacologic inhibition of ASK1 could attenuate hepatic fibrosis driven by inflammasome activation using gain-of-function NOD-like receptor protein 3 (Nlrp3) mutant mice. Tamoxifen-inducible Nlrp3 knock-in (Nlrp3A350V/+CreT-KI) mice and WT mice were administered either control chow diet or diet containing the selective ASK1 inhibitor GS-444217 for 6 weeks. Livers of Nlrp3-KI mice had increased inflammation, cell death, and fibrosis and increased phosphorylation of ASK1, p38, and c-Jun. GS-444217 reduced ASK1 pathway activation, liver cell death, and liver fibrosis. ASK1 inhibition resulted in a significant downregulation of genes involved in collagen production and extracellular matrix deposition, as well as in a reduced hepatic TNF-α expression. ASK1 inhibition also directly reduced LPS-induced gene expression of Collagen 1A1 (Col1a1) in hepatic stellate cells isolated from Nlrp3-KI mice. In conclusion, ASK1 inhibition reduced liver cell death and fibrosis downstream of inflammatory signaling induced by NLRP3. These data provide mechanistic insight into the antifibrotic mechanisms of ASK1 inhibition.
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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.