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Ann Hepatol ; 29(5): 101517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38852781

RESUMO

INTRODUCTION AND OBJECTIVES: Liver fibrosis remains a complication derived from a chronic Hepatitis C Virus (HCV) infection even when it is resolved, and no liver antifibrotic drug has been approved. Molecular mechanisms on hepatocytes and activation of hepatic stellate cells (HSCs) play a central role in liver fibrogenesis. To elucidate molecular mechanisms, it is important to analyze pathway regulation during HSC activation and HCV infection. MATERIALS AND METHODS: We evaluate the fibrosis-associated molecular mechanisms during a co-culture of human HSCs (LX2), with human hepatocytes (Huh7) that express HCV NS5A or Core protein. We evaluated LX2 activation induced by HCV NS5A or Core expression in Huh7 cells during co-culture. We determined a fibrosis-associated gene expression profile in Huh7 that expresses NS5A or Core proteins during the co-culture with LX2. RESULTS: We observed that NS5A induced 8.3-, 6.7- and 4-fold changes and that Core induced 6.5-, 1.8-, and 6.2-fold changes in the collagen1, TGFß1, and timp1 gene expression, respectively, in LX2 co-cultured with transfected Huh7. In addition, NS5A induced the expression of 30 genes while Core induced 41 genes and reduced the expression of 30 genes related to fibrosis in Huh7 cells during the co-culture with LX2, compared to control. The molecular pathways enriched from the gene expression profile were involved in TGFB signaling and the organization of extracellular matrix. CONCLUSIONS: We demonstrated that HCV NS5A and Core protein expression regulate LX2 activation. NS5A and Core-induced LX2 activation, in turn, regulates diverse fibrosis-related gene expression at different levels in Huh7, which can be further analyzed as potential antifibrotic targets during HCV infection.


Assuntos
Técnicas de Cocultura , Colágeno Tipo I , Hepacivirus , Células Estreladas do Fígado , Hepatócitos , Cirrose Hepática , Inibidor Tecidual de Metaloproteinase-1 , Fator de Crescimento Transformador beta1 , Proteínas do Core Viral , Proteínas não Estruturais Virais , Humanos , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Hepacivirus/genética , Hepatócitos/metabolismo , Hepatócitos/virologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Proteínas do Core Viral/genética , Proteínas do Core Viral/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Regulação da Expressão Gênica , Transdução de Sinais , Cadeia alfa 1 do Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I/metabolismo , Perfilação da Expressão Gênica/métodos , Linhagem Celular Tumoral , RNA Polimerase Dependente de RNA
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