Nikoletta Argentou1, Georgios Germanidis2, Prodromos Hytiroglou3, Eirini Apostolou4, Themistoklis Vassiliadis5, Kalliopi Patsiaoura6, Paschalis Sideras4, Anastasios E Germenis1, Matthaios Speletas7. 1. Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Biopolis, 41500, Larissa, Greece. 2. First Department of Internal Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, School of Medicine, 54636, Thessaloniki, Greece. 3. Department of Pathology, AHEPA Hospital, Aristotle University of Thessaloniki, School of Medicine, Kyriakidi Str. 1, 54636, Thessaloniki, Greece. 4. Centre for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, 11527, Athens, Greece. 5. Third Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, 56403, Thessaloniki, Greece. 6. Department of Pathology, Hippokration Hospital, 54635, Thessaloniki, Greece. 7. Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Biopolis, 41500, Larissa, Greece. maspel@med.uth.gr.
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.
OBJECTIVES: Although animal studies demonstrated that Smad7 induction ameliorates TGF-β/SMAD-mediated fibrogenesis, its role in humanhepatic 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 humanhepatic diseases; therefore, SMAD7 induction likely represents a candidate for novel therapeutic approaches.
Authors: Rebecca T Marquez; Sarmistha Bandyopadhyay; Erik B Wendlandt; Kathy Keck; Brandon A Hoffer; Michael S Icardi; Randolph N Christensen; Warren N Schmidt; Anton P McCaffrey Journal: Lab Invest Date: 2010-07-12 Impact factor: 5.662
Authors: K Ishak; A Baptista; L Bianchi; F Callea; J De Groote; F Gudat; H Denk; V Desmet; G Korb; R N MacSween Journal: J Hepatol Date: 1995-06 Impact factor: 25.083
Authors: Mohamed Tarek M Shata; Enass A Abdel-Hameed; Susan D Rouster; Li Yu; Meina Liang; Esther Song; Mark T Esser; Norah Shire; Kenneth E Sherman Journal: Pathog Immun Date: 2019-02-13