TGF-β signaling is activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment.
Τίτλος | TGF-β signaling is activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Argentou, N., Germanidis G., Hytiroglou P., Apostolou E., Vassiliadis T., Patsiaoura K., Sideras P., Germenis A. E., & Speletas M. |
Journal | Inflamm Res |
Volume | 65 |
Issue | 5 |
Pagination | 355-65 |
Date Published | 2016 May |
ISSN | 1420-908X |
Λέξεις κλειδιά | Adult, Aged, Antiviral Agents, Chronic Disease, Female, Fibrosis, Hepatitis B, Hepatitis C, Humans, Liver, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, RNA, Messenger, Signal Transduction, Smad7 Protein, Transforming Growth Factor beta, Young Adult |
Abstract | OBJECTIVES: Although animal studies demonstrated that Smad7 induction ameliorates TGF-β/SMAD-mediated fibrogenesis, its role in human hepatic diseases is rather obscure. Our study explored the activation status of TGF-β/activin pathway in patients with chronic liver diseases, and how it is affected by successful antiviral treatment in chronic HBV hepatitis (CHB).METHODS: Thirty-seven CHB patients (19 with active disease, 14 completely remitted on long-term antiviral treatment and 4 with relapse after treatment withdrawal), 18 patients with chronic HCV hepatitis, 12 with non-alcoholic fatty liver disease (NAFLD), and 3 controls were enrolled in the study. Liver mRNA levels of CTGF, all TGF-β/activin isoforms, their receptors and intracellular mediators (SMADs) were evaluated using qRT-PCR and were correlated with the grade of liver inflammation and fibrosis staging. The expression and localization of pSMAD2 and pSMAD3 were assessed by immunohistochemistry.RESULTS: TGF-β signalling is activated in CHB patients with active disease, while SMAD7 is up-regulated during the resolution of inflammation after successful treatment. SMAD7 overexpression was also observed in NAFLD patients exhibiting no or minimal fibrosis, despite the activation of TGF-β/activin signaling.CONCLUSIONS: SMAD7 overexpression might represent a mechanism limiting TGF-β-mediated fibrogenesis in human hepatic diseases; therefore, SMAD7 induction likely represents a candidate for novel therapeutic approaches. |
DOI | 10.1007/s00011-016-0921-6 |
Alternate Journal | Inflamm. Res. |
PubMed ID | 26856334 |