TGF-β signaling is activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment.

Autor: Argentou N; Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Biopolis, 41500, Larissa, Greece., Germanidis G; First Department of Internal Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, School of Medicine, 54636, Thessaloniki, Greece., Hytiroglou P; Department of Pathology, AHEPA Hospital, Aristotle University of Thessaloniki, School of Medicine, Kyriakidi Str. 1, 54636, Thessaloniki, Greece., Apostolou E; Centre for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, 11527, Athens, Greece., Vassiliadis T; Third Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, 56403, Thessaloniki, Greece., Patsiaoura K; Department of Pathology, Hippokration Hospital, 54635, Thessaloniki, Greece., Sideras P; Centre for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, 11527, Athens, Greece., Germenis AE; Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Biopolis, 41500, Larissa, Greece., Speletas M; Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Biopolis, 41500, Larissa, Greece. maspel@med.uth.gr.
Jazyk: angličtina
Zdroj: Inflammation research : official journal of the European Histamine Research Society ... [et al.] [Inflamm Res] 2016 May; Vol. 65 (5), pp. 355-65. Date of Electronic Publication: 2016 Feb 09.
DOI: 10.1007/s00011-016-0921-6
Abstrakt: 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.
Databáze: MEDLINE
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