ArticleHepatology (Baltimore, Md.)2014
Paracrine signals from liver sinusoidal endothelium regulate hepatitis C virus replication.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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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.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Liver sinusoidal endothelial cells in liver diseases and hepatocellular carcinoma: molecular mechanisms, physiology, and therapies.Molecular biomedicine · 2026Review
- Serum Gremlin 1 Remains Elevated Following Successful Direct-Acting Antiviral Therapy for Chronic Hepatitis C.Viruses · 2026Article
- Interleukin 33 Promotes Liver Sinusoidal Endothelial Cell Dysfunction and Hepatic Fibrosis in Diabetic Mice.Diabetes & metabolism journal · 2025Article
- Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis.Clinical and molecular hepatology · 2024Review
- Hepatitis B Virus Targets Lipid Transport Pathways to Infect Hepatocytes.Cellular and molecular gastroenterology and hepatology · 2023Article
- Role of liver sinusoidal endothelial cells in liver diseases.Nature reviews. Gastroenterology & hepatology · 2021Review
- Gene signatures of SARS-CoV/SARS-CoV-2-infected ferret lungs in short- and long-term models.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Article
- Review
- BMP4-mediated autophagy is involved in the metastasis of hepatocellular carcinomaAmerican journal of translational research · 2020Article
- The Role of Sinusoidal Endothelial Cells in the Axis of Inflammation and Cancer Within the Liver.Frontiers in physiology · 2020Review
- Liver sinusoidal endothelial cells - gatekeepers of hepatic immunity.Nature reviews. Gastroenterology & hepatology · 2018Review
- Transcriptomic Analysis of Hepatic Cells in Multicellular Organotypic Liver Models.Scientific reports · 2018Article
- BMP Signalling at the Crossroad of Liver Fibrosis and Regeneration.International journal of molecular sciences · 2017Review
- [Liver sinusoidal endothelial cells regulate adaptive immune tolerance in the liver].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2017Review
- Organ system view of the hepatic innate immunity in HCV infection.Journal of medical virology · 2016Review
- Effect of scavenger receptor class B type I antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2016Article
- Angiogenesis and liver fibrosis.World journal of hepatology · 2015Review
- Hepatitis C virus infection induces autocrine interferon signaling by human liver endothelial cells and release of exosomes, which inhibits viral replication.Gastroenterology · 2015Article
- Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication.Clinical science (London, England : 1979) · 2014Article
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11 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledHepatitis C virus (HCV) is a major cause of global morbidity, causing chronic liver injury that can progress to cirrhosis and hepatocellular carcinoma. The liver is a large and complex organ containing multiple cell types, including hepatocytes, sinusoidal endothelial cells (LSEC), Kupffer cells, and biliary epithelial cells. Hepatocytes are the major reservoir supporting HCV replication; however, the role of nonparenchymal cells in the viral lifecycle remains largely unexplored. LSEC secrete factors that promote HCV infection and transcript analysis identified bone morphogenetic protein 4 (BMP4) as a candidate endothelial-expressed proviral molecule. Recombinant BMP4 increased HCV replication and neutralization of BMP4 abrogated the proviral activity of LSEC-conditioned media. Importantly, BMP4 expression was negatively regulated by vascular endothelial growth factor A (VEGF-A) by way of a VEGF receptor-2 (VEGFR-2) primed activation of p38 MAPK. Consistent with our in vitro observations, we demonstrate that in normal liver VEGFR-2 is activated and BMP4 expression is suppressed. In contrast, in chronic liver disease including HCV infection where there is marked endothelial cell proliferation, we observed reduced endothelial cell VEGFR-2 activation and a concomitant increase in BMP4 expression.
conclusionThese studies identify a role for LSEC and BMP4 in HCV infection and highlight BMP4 as a new therapeutic target for treating individuals with liver disease.
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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.