ArticlePloS one2012
Inhibition of Notch signaling by a γ-secretase inhibitor attenuates hepatic fibrosis in rats.
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 83 papers.
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Who cites it
83 citing papers in PubMed, 139 citations in OpenAlex.
- Cell differentiation-related signaling pathways: biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Niche-associated Type IV collagen promotes GLP-1/Notch receptor activation in the C. elegans germline.Nature communications · 2025Article
- Dibenzazepine, a γ-Secretase Enzyme Inhibitor, Protects Against Doxorubicin-Induced Cardiotoxicity by Suppressing NF-κB, iNOS, and Hes1/Hey1 Expression.Inflammation · 2025Article
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Beyond glycemic control: the cardiac and hepatic benefits of SGLT2 and DPP-4 inhibitors in mitigating chronic cadmium-induced inflammation, oxidative/nitrative stress, apoptosis and fibrosis.Frontiers in physiology · 2025Article
- The IGF2BP3/Notch/Jag1 pathway: A key regulator of hepatic stellate cell ferroptosis in liver fibrosis.Clinical and translational medicine · 2024Article
- Evaluation of different media compositions promoting hepatocyte differentiation in the canine liver organoid model.Heliyon · 2024Article
- Resveratrol treatment ameliorates hepatic damage via the TGF-β/SMAD signaling pathway in a phenobarbital/CClIranian journal of basic medical sciences · 2024Article
- Modulation of Notch signaling pathway in activated hepatic stellate cells does not ameliorate the outcome of liver fibrosis in carbon tetrachloride and DDC-feeding models.Frontiers in pharmacology · 2024Article
- The role of ischaemia-reperfusion injury and liver regeneration in hepatic tumour recurrence.JHEP reports : innovation in hepatology · 2023Review
- Characterization of human stem cell-derived hepatic stellate cells and liver sinusoidal endothelial cells during extendedFrontiers in bioengineering and biotechnology · 2023Article
- Jagged-1/Notch Pathway and Key Transient Markers Involved in Biliary Fibrosis duringTropical medicine and infectious disease · 2022Article
- Combined resveratrol and vitamin D treatment ameliorate inflammation-related liver fibrosis, ER stress, and apoptosis in a high-fructose diet/streptozotocin-induced T2DM model.Histochemistry and cell biology · 2022Article
- Tamoxifen Ameliorates Cholestatic Liver Fibrosis in Mice: Upregulation of TGFβ and IL6 Is a Potential Protective Mechanism.Biomedicines · 2022Article
- Lingonberry Improves Hepatic Lipid Metabolism by Targeting Notch1 Signaling.Antioxidants (Basel, Switzerland) · 2022Article
- Engineering Modular 3D Liver Culture MicroenvironmentsAdvanced nanobiomed research · 2022Article
- Review
- MiR-571 affects the development and progression of liver fibrosis by regulating the Notch3 pathway.Scientific reports · 2021Article
- Article
- The TGFβ/Notch axis facilitates Müller cell-to-epithelial transition to ultimately form a chronic glial scar.Molecular neurodegeneration · 2021Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling is essential to the regulation of cell differentiation, and aberrant activation of this pathway is implicated in human fibrotic diseases, such as pulmonary, renal, and peritoneal fibrosis. However, the role of Notch signaling in hepatic fibrosis has not been fully investigated. In the present study, we show Notch signaling to be highly activated in a rat model of liver fibrosis induced by carbon tetrachloride (CCl(4)), as indicated by increased expression of Jagged1, Notch3, and Hes1. Blocking Notch signaling activation by a γ-secretase inhibitor, DAPT, significantly attenuated liver fibrosis and decreased the expression of snail, vimentin, and TGF-β1 in association with the enhanced expression of E-cadherin. The study in vitro revealed that DAPT treatment could suppress the EMT process of rat hepatic stellate cell line (HSC-T6). Interestingly, DAPT treatment was found not to affect hepatocyte proliferation in vivo. In contrast, DAPT can inhibit hepatocyte apoptosis to some degree. Our study provides the first evidence that Notch signaling is implicated in hepatic fibrogenesis and DAPT treatment has a protective effect on hepatocytes and ameliorates liver fibrosis. These findings suggest that the inhibition of Notch signaling might present a novel therapeutic approach for hepatic 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.