ArticleJournal of virology2012
Hepatitis C virus activates Bcl-2 and MMP-2 expression through multiple cellular signaling pathways.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Clinical Significance of MYBL2 Expression in Hepatocellular Carcinoma: Impact on Overall Survival.OncoTargets and therapy · 2025Article
- Resveratrol Enhances Antioxidant and Anti-Apoptotic Capacities in Chicken Primordial Germ Cells through m6A Methylation: A Preliminary Investigation.Animals : an open access journal from MDPI · 2024Article
- Porcine alveolar macrophages host proteins interacting with African swine fever virus p72.Frontiers in microbiology · 2024Article
- The Transgene Expression of the Immature Form of the HCV Core Protein (C191) and the LncRNA MEG3 Increases Apoptosis in HepG2 Cells.Current issues in molecular biology · 2022Article
- Article
- Molecular Crosstalk between the Hepatitis C Virus and the Extracellular Matrix in Liver Fibrogenesis and Early Carcinogenesis.Cancers · 2021Review
- Profibrotic Signaling and HCC Risk during Chronic Viral Hepatitis: Biomarker Development.Journal of clinical medicine · 2021Review
- Viral hijacking of host caspases: an emerging category of pathogen-host interactions.Cell death and differentiation · 2017Review
- How Hepatitis C Virus Leads to Hepatocellular Carcinoma: A Network-Based Study.Hepatitis monthly · 2016Article
- SOCS3 mRNA expression and polymorphisms as pretreatment predictor of response to HCV genotype 3a IFN-based treatment.SpringerPlus · 2016Article
- JNK1 Derived from Orange-Spotted Grouper, Epinephelus coioides, Involving in the Evasion and Infection of Singapore Grouper Iridovirus (SGIV).Frontiers in microbiology · 2016Article
- A New Signaling Pathway for HCV Inhibition by Estrogen: GPR30 Activation Leads to Cleavage of Occludin by MMP-9.PloS one · 2016Article
- Article
- Hepatitis C virus-mediated angiogenesis: molecular mechanisms and therapeutic strategies.World journal of gastroenterology · 2014Review
- Mechanisms of HCV-induced liver cancer: what did we learn from in vitro and animal studies?Cancer letters · 2014Review
- Disruption of Bcl-2 and Bcl-xL by viral proteins as a possible cause of cancer.Infectious agents and cancer · 2014Review
- ERK signaling is triggered by hepatitis C virus E2 protein through DC-SIGN.Cell stress & chaperones · 2013Article
- Hepatocellular Carcinoma in Asia: A Challenging Situation.Euroasian journal of hepato-gastroenterologyReview
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) infection is associated with numerous liver diseases and causes serious global health problems, but the mechanisms underlying the pathogenesis of HCV infections remain largely unknown. In this study, we demonstrate that signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-2 (MMP-2), and B-cell lymphoma 2 (Bcl-2) are significantly stimulated in HCV-infected patients. We further show that HCV activates STAT3, MMP-2, Bcl-2, extracellular regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK) in infected Huh7.5.1 cells. Functional screening of HCV proteins revealed that nonstructural protein 4B (NS4B) is responsible for the activation of MMP-2 and Bcl-2 by stimulating STAT3 through repression of the suppressor of cytokine signaling 3 (SOCS3). Our results also demonstrate that multiple signaling cascades, including several members of the protein kinase C (PKC) family, JNK, ERK, and STAT3, play critical roles in the activation of MMP-2 and Bcl-2 mediated by NS4B. Further studies revealed that the C-terminal domain (CTD) of NS4B is sufficient for the activation of STAT3, JNK, ERK, MMP-2, and Bcl-2. We also show that amino acids 227 to 250 of NS4B are essential for regulation of STAT3, JNK, ERK, MMP-2, and Bcl-2, and among them, three residues (237L, 239S, and 245L) are crucial for this regulation. Thus, we reveal a novel mechanism underlying HCV pathogenesis in which multiple intracellular signaling cascades are cooperatively involved in the activation of two important cellular factors, MMP-2 and Bcl-2, in response to HCV infection.
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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.