Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells



Document title: Pegylated interferon-α2b and ribavirin decrease claudin-1 and E-cadherin expression in HepG2 and Huh-7.5 cells
Journal: Annals of hepatology
Database: PERIÓDICA
System number: 000415688
ISSN: 1665-2681
Authors: 1
1
2
3
4
1
1
Institutions: 1Universidad Nacional Autónoma de México, Facultad de Medicina, México, Distrito Federal. México
2Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, México, Distrito Federal. México
3Universidad Autónoma de Nuevo León, Facultad de Medicina, Monterrey, Nuevo León. México
4Instituto Nacional de Cardiología Ignacio Chávez, Departamento de Fisiología, México, Distrito Federal. México
Year:
Season: Jul-Ago
Volumen: 12
Number: 4
Pages: 448-457
Country: México
Language: Inglés
Document type: Artículo
Approach: Analítico, descriptivo
English abstract Hepatitis C virus (HCV) infection usually results in long-term viremia. Entry of HCV into the hepatocyte requires claudin-1, -6, -9 and occludin. The efficacy of Pegylated interferon-α (PEG-IFN) treatment against HCV infection increased when ribavirin (RBV) was added to the therapeutic scheme. Our aim was to investigate if PEG-IFN plus RBV regulate claudin expression. Material and methods. HepG2, Huh-7 and Huh-7.5 cells were treated with PEG-IFN-α2a or α2b and/or RBV at different times before obtaining the cytosolic, membrane and cytoskeletal fractions. Claudin-1, 3, 4, 6, and 9, E-cadherin and occludin expression was evaluated by Western blot analysis. Transepithelial electrical resistance (TER) was also determined. Results. Claudin-1, 3, 4, 6, E-cadherin and occludin are constitutively expressed mainly in HepG2 cell membrane. Claudin-1 and E-cadherin cell membrane expression diminished after exposure to PEGIFNα2b (50 ng) + RBV(50 µg); the maximal decrease was observed with 200 ng of PEG-IFNα2b + 200 µg of RBV. The effect was less intense with PEG-IFNα2a. The inhibition of claudin-1 and E-cadherin expression in Huh-7 and Huh-7.5 cells was only observed with 200 ng of PEG-IFNα2b + 200 µg of RBV. TER diminished marginally in the HCV containing hepatoma cells with 200 ng of PEG-IFNα2b + 200 µg of RBV. Claudin-1 mRNA expression level was not affected by the combined treatment. Conclusion. The increased therapeutic efficacy of the PEG-IFNα2b plus RBV treatment could be secondary to the inhibition of claudin-1 and E-cadherin cell membrane expression
Disciplines: Medicina
Keyword: Gastroenterología,
Virus de la hepatitis C,
Interferón pegilado,
Ribavirina,
Claudinas,
Cadherinas
Keyword: Medicine,
Gastroenterology,
Hepatitis C virus,
Pegylated interferon,
Ribavirin,
Claudins,
Cadherins
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