ArticleJournal of hepatology2013
The AMPK-related kinase SNARK regulates hepatitis C virus replication and pathogenesis through enhancement of TGF-β signaling.
Article in Journal of hepatology, 2013. 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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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- HBV promotes epithelial-mesenchymal transition in HCC and liver fibrosis through JNK-mediated autophagy.Hepatology communications · 2025Article
- c-Met inhibitor NVP-BVU972 induces antiviral protection and suppresses NF-κB-mediated inflammation.Frontiers in immunology · 2025Article
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- SARS-CoV-2 Lysate Stimulation Impairs the Release of Platelet-like Particles and Megakaryopoiesis in the MEG-01 Cell Line.International journal of molecular sciences · 2023Article
- NUAK Kinases: Brain-Ovary Axis.Cells · 2021Review
- AMPKα-like proteins as LKB1 downstream targets in cell physiology and cancer.Journal of molecular medicine (Berlin, Germany) · 2021Review
- The Role of AMP-Activated Protein Kinase as a Potential Target of Treatment of Hepatocellular Carcinoma.Cancers · 2019Review
- Transforming growth factor β (TGFβ) induces NUAK kinase expression to fine-tune its signaling output.The Journal of biological chemistry · 2019Article
- Sucrose nonfermenting AMPK-related kinase (SNARK) regulates exercise-stimulated and ischemia-stimulated glucose transport in the heart.Journal of cellular biochemistry · 2019Article
- Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro.Stem cells international · 2019Article
- AMP-Activated Protein Kinase and Host Defense against Infection.International journal of molecular sciences · 2018Review
- Novel therapeutic features of disulfiram against hepatocellular carcinoma cells with inhibitory effects on a disintegrin and metalloproteinase 10.Oncotarget · 2018Article
- Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase.Oncotarget · 2017Article
- Novel chemoimmunotherapeutic strategy for hepatocellular carcinoma based on a genome-wide association study.Scientific reports · 2016Article
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- AMPK Inhibits the Stimulatory Effects of TGF-β on Smad2/3 Activity, Cell Migration, and Epithelial-to-Mesenchymal Transition.Molecular pharmacology · 2015Article
- MICA SNPs and the NKG2D system in virus-induced HCC.Journal of gastroenterology · 2015Review
- Diabetes and Hepatitis C: A Two-Way Association.Frontiers in endocrinology · 2015Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsHepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. The biological and therapeutic importance of host cellular cofactors for viral replication has been recently appreciated. Here we examined the roles of SNF1/AMP kinase-related kinase (SNARK) in HCV replication and pathogenesis.
methodsThe JFH1 infection system and the full-length HCV replicon OR6 cell line were used. Gene expression was knocked down by siRNAs. SNARK mutants were created by site-directed mutagenesis. Intracellular mRNA levels were measured by qRT-PCR. Endogenous and overexpressed proteins were detected by Western blot analysis and immunofluorescence. Transforming growth factor (TGF)-β signaling was monitored by a luciferase reporter construct. Liver biopsy samples from HCV-infected patients were analyzed for SNARK expression.
resultsKnockdown of SNARK impaired viral replication, which was rescued by wild type SNARK but not by unphosphorylated or kinase-deficient mutants. Knockdown and overexpression studies demonstrated that SNARK promoted TGF-β signaling in a manner dependent on both its phosphorylation and kinase activity. In turn, chronic HCV replication upregulated the expression of SNARK in patients. Further, the SNARK kinase inhibitor metformin suppressed both HCV replication and SNARK-mediated enhancement of TGF-β signaling.
conclusionsThus reciprocal regulation between HCV and SNARK promotes TGF-β signaling, a major driver of hepatic fibrogenesis. These findings suggest that SNARK will be an attractive target for the design of novel host-directed antiviral and antifibrotic drugs.
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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.