ArticleJournal of immunology (Baltimore, Md. : 1950)2022
Hepatitis B and Hepatitis C Virus Infection Promote Liver Fibrogenesis through a TGF-β1-Induced OCT4/Nanog Pathway.
Article in Journal of immunology (Baltimore, Md. : 1950), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Association between PNPLA3 rs738409 and susceptibility to etiology-specific liver cirrhosis: a systematic review and meta-analysis.BMC medical genomics · 2026Pooled it
- Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026Review
- A Unified Histopathological Framework of Liver Fibrogenesis in Chronic Viral Hepatitis B, C and Coinfection.Diseases (Basel, Switzerland) · 2026Article
- Modeling hepatic fibrosis in TP53 knockout iPSC-derived human liver organoids.Molecular oncology · 2026Article
- The role of liver macrophages in viral liver pathogenesis.Journal of leukocyte biology · 2025Review
- HBV promotes epithelial-mesenchymal transition in HCC and liver fibrosis through JNK-mediated autophagy.Hepatology communications · 2025Article
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- Circulating let-7 Predicts Hepatic Fibrogenesis of 12-Month Post-Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus.The Kaohsiung journal of medical sciences · 2025Article
- Integrative analysis of serum proteomics and transcriptomics in hepatitis C.Virology journal · 2025Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- In Vivo and In Vitro Models of Hepatic Fibrosis for Pharmacodynamic Evaluation and Pathology Exploration.International journal of molecular sciences · 2025Review
- Single-nucleus RNA sequencing reveals HBV-driven metabolic reprogramming and TIMP1-mediated fibrosis in human-liver-chimeric mice.Frontiers in cellular and infection microbiology · 2025Article
- Antiviral Effects and Mechanisms of Active Ingredients in Tea.Molecules (Basel, Switzerland) · 2024Review
- HIV coinfection exacerbates HBV-induced liver fibrogenesis through a HIF-1α- and TGF-β1-dependent pathway.Journal of hepatology · 2024Article
- Multifunctional roles of inflammation and its causative factors in primary liver cancer: A literature review.World journal of hepatology · 2023Review
- Serum Alpha-Fetoprotein as a Predictor of Liver Fibrosis in HBeAg-Positive Chronic Hepatitis B Patients.Medicina (Kaunas, Lithuania) · 2023Article
- Insights into the impact of hepatitis B virus on hepatic stellate cell activation.Cell communication and signaling : CCS · 2023Review
- Roles of TGF-β1 in Viral Infection during Pregnancy: Research Update and Perspectives.International journal of molecular sciences · 2023Review
- Influence of the At-Arrival Host Transcriptome on Bovine Respiratory Disease Incidence during Backgrounding.Veterinary sciences · 2023Article
- A Comprehensive Hepatitis B Surface Antigen-Positive Patient-Centered Screening and Linkage to Care Strategies Targeting Microelimination of Hepatitis C Virus Infection in Chongqing, China.Canadian journal of gastroenterology & hepatology · 2022Observational
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection accelerates liver fibrosis progression compared with HBV or HCV monoinfection. Octamer binding transcription factor 4 (OCT4) and Nanog are direct targets of the profibrogenic TGF-β1 signaling cascade. We leveraged a coculture model to monitor the effects of HBV and HCV coinfection on fibrogenesis in both sodium taurocholate cotransporting polypeptide-transfected Huh7.5.1 hepatoma cells and LX2 hepatic stellate cells (HSCs). We used CRISPR-Cas9 to knock out OCT4 and Nanog to evaluate their effects on HBV-, HCV-, or TGF-β1-induced liver fibrogenesis. HBV/HCV coinfection and HBx, HBV preS2, HCV Core, and HCV NS2/3 overexpression increased TGF-β1 mRNA levels in sodium taurocholate cotransporting polypeptide-Huh7.5.1 cells compared with controls. HBV/HCV coinfection further enhanced profibrogenic gene expression relative to HBV or HCV monoinfection. Coculture of HBV and HCV monoinfected or HBV/HCV coinfected hepatocytes with LX2 cells significantly increased profibrotic gene expression and LX2 cell invasion and migration. OCT4 and Nanog guide RNA independently suppressed HBV-, HCV-, HBV/HCV-, and TGF-β1-induced α-SMA, TIMP-1, and Col1A1 expression and reduced Huh7.5.1, LX2, primary hepatocyte, and primary human HSC migratory capacity. OCT4/Nanog protein expression also correlated positively with fibrosis stage in liver biopsies from patients with chronic HBV or HCV infection. In conclusion, HBV and HCV independently and cooperatively promote liver fibrogenesis through a TGF-β1-induced OCT4/Nanog-dependent pathway.
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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.