ArticleHepatology communications2017
Identification of a novel alpha-fetoprotein-expressing cell population induced by the Jagged1/Notch2 signal in murine fibrotic liver.
Article in Hepatology communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Organ-Specific Dedifferentiation and Epigenetic Remodeling in In Vivo Reprogramming.Aging cell · 2025Review
- Pay attention to the value of liver regeneration in the re-compensation of decompensated cirrhosis.World journal of gastroenterology · 2025Review
- Jag1 insufficiency alters liver fibrosis via T cell and hepatocyte differentiation defects.EMBO molecular medicine · 2024Article
- Serum Alpha-Fetoprotein as a Predictor of Liver Fibrosis in HBeAg-Positive Chronic Hepatitis B Patients.Medicina (Kaunas, Lithuania) · 2023Article
- Mitochondrial dysfunction reactivates α-fetoprotein expression that drives copper-dependent immunosuppression in mitochondrial disease models.The Journal of clinical investigation · 2023Article
- Saffron reduces the liver fibrosis in mice by inhibiting the JAK/STAT3 pathway.Acta cirurgica brasileira · 2023Article
- Cellular heterogeneity and plasticity during NAFLD progression.Frontiers in molecular biosciences · 2023Review
- In vivo partial cellular reprogramming enhances liver plasticity and regeneration.Cell reports · 2022Article
- Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease.Disease models & mechanisms · 2022Article
- Two distinct Notch signals, Delta-like 4/Notch1 and Jagged-1/Notch2, antagonistically regulate chemical hepatocarcinogenesis in mice.Communications biology · 2022Article
- Features of patients who developed hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C Virus.PloS one · 2022Observational
- Blood-Based Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma, Including the Viral Genome and Glycosylated Proteins.International journal of molecular sciences · 2021Review
- Serum alpha-fetoprotein increases prior to fibrosis resolution in a patient with acute liver failure.Clinical journal of gastroenterology · 2021Article
- Hepatocyte TLR4 triggers inter-hepatocyte Jagged1/Notch signaling to determine NASH-induced fibrosis.Science translational medicine · 2021Article
- Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration.JCI insight · 2020Article
- Fate and functional roles of Prominin 1Scientific reports · 2020Article
- Early identification using the referral system prolonged the time to onset for hepatic encephalopathy after diagnosing severe acute liver injury.Scientific reports · 2020Observational
- Mesenchymal stem cells activate Notch signaling to induce regulatory dendritic cells in LPS-induced acute lung injury.Journal of translational medicine · 2020Article
- TGF-β1 signaling activates hepatic stellate cells through Notch pathway.Cytotechnology · 2019Article
- Carvedilol attenuates carbon tetrachloride-induced liver fibrosis and hepatic sinusoidal capillarization in mice.Drug design, development and therapy · 2019Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver is well known to possess high regenerative capacity in response to partial resection or tissue injury. However, liver regeneration is often impaired in the case of advanced liver fibrosis/cirrhosis when mature hepatocytes can hardly self-proliferate. Hepatic progenitor cells have been implicated as a source of hepatocytes in regeneration of the fibrotic liver. Although alpha-fetoprotein (AFP) is known as a clinical marker of progenitor cell induction in injured/fibrotic adult liver, the origin and features of such AFP-producing cells are not fully understood. Here, we demonstrate a unique and distinct AFP-expressing cell population that is induced by the Jagged1/Notch2 signal in murine fibrotic liver. Following repeated carbon tetrachloride injections, a significant number of AFP-positive cells with high proliferative ability were observed along the fibrous septa depending on the extent of liver fibrosis. These AFP-positive cells exhibited features of immature hepatocytes that were stained positively for hepatocyte-lineage markers, such as albumin and hepatocyte nuclear factor 4 alpha, and a stem/progenitor cell marker Sox9. A combination of immunohistological examination of fibrotic liver tissues and coculture experiments with primary hepatocytes and hepatic stellate cells indicated that increased Jagged1 expression in activated hepatic stellate cells stimulated Notch2 signaling and up-regulated AFP expression in adjacent hepatocytes. The mobilization and proliferation of AFP-positive cells in fibrotic liver were further enhanced after partial hepatectomy, which was significantly suppressed in Jagged1-conditional knockout mice. Finally, forced expression of the intracellular domain of Notch2 in normal liver induced a small number of AFP-expressing hepatocytes
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