ArticleScientific reports2015
The interplay of the Notch signaling in hepatic stellate cells and macrophages determines the fate of liver fibrogenesis.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials.Clinical and translational medicine · 2024Pooled it
- Decoding fibroblast activation: Transcriptional networks in hepatic stellate cells and across fibrotic organs (Review).International journal of molecular medicine · 2026Review
- TGF-β-induced fibrotic scar formation limits recovery of spinal cord injury.Bone research · 2026Article
- From genome to drug targets: computational subtractive genomics reveals novel anti-filarial targets in Wuchereria bancrofti and identifies plant-based inhibitors of β-1,4-mannosyltransferase, a high-priority target.Molecular diversity · 2026Article
- Review
- Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages.Frontiers in immunology · 2026Review
- Iron-related intercellular communication in the liver: Main players and mechanisms.European journal of clinical investigation · 2026Review
- Biliary atresia-related liver fibrosis.Frontiers in cell and developmental biology · 2026Review
- Review
- Hepatic stellate cells in liver fibrosis: From biology to pathology.Open veterinary journal · 2025Review
- Unravelling the reversion mechanisms of activated hepatic stellate cell properties by extracellular vesicles from mesenchymal stem cells.World journal of stem cells · 2025Review
- Role of immune cell subsets in liver fibrosis through single-cell RNA sequencing and array.Cancer biomarkers : section A of Disease markers · 2025Article
- Effects of wasabi (Toxicology research · 2025Article
- Notch1 siRNA and AMD3100 Ameliorate Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2025Article
- A novel 11β-HSD1 inhibitor ameliorates liver fibrosis by inhibiting the notch signaling pathway and increasing NK cell population.Archives of pharmacal research · 2025Article
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The IGF2BP3/Notch/Jag1 pathway: A key regulator of hepatic stellate cell ferroptosis in liver fibrosis.Clinical and translational medicine · 2024Article
- Consequences of Amyloid-β Deficiency for the Liver.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A detailed overview of quercetin: implications for cell death and liver fibrosis mechanisms.Frontiers in pharmacology · 2024Review
- Communication molecules (ncRNAs) mediate tumor-associated macrophage polarization and tumor progression.Frontiers in cell and developmental biology · 2024Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic stellate cells (HSCs) known as "master producers" and macrophages as "master regulators", are the key cell types that strongly contribute to the progression of liver fibrosis. Since Notch signaling regulates multiple cellular processes, we aimed to study the role of Notch signaling in HSCs differentiation and macrophages polarization and to evaluate its implication in liver fibrogenesis. Notch pathway components were found to be significantly upregulated in TGFβ-activated HSCs, inflammatory M1 macrophages, and in mouse and human fibrotic livers. Interestingly, inhibition of Notch using a selective γ-secretase inhibitor, Avagacestat, significantly inhibited TGFβ-induced HSC activation and contractility, and suppressed M1 macrophages. Additionally, Avagacestat inhibited M1 driven-fibroblasts activation and fibroblasts-driven M1 polarization (nitric oxide release) in fibroblasts and macrophages co-culture, and conditioned medium studies. In vivo, post-disease treatment with Avagacestat significantly attenuated fibrogenesis in CCl4-induced liver fibrosis mouse model. These effects were attributed to the reduction in HSCs activation, and inhibition of inflammatory M1 macrophages and upregulation of suppressive M2 macrophages. These findings suggest that Notch signaling plays a crucial role in HSC activation and M1/M2 polarization of macrophages in liver fibrosis. These results provide new insights for the development of novel therapies against liver fibrosis through modulation of Notch signaling.
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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.