title: TGF-β signaling is activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment.
abstract: OBJECTIVE
  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.
authors: Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Biopolis, 41500, Larissa, Greece.
authors: Nikoletta
authors: N
authors: Argentou
authors: First Department of Internal Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, School of Medicine, 54636, Thessaloniki, Greece.
authors: Georgios
authors: G
authors: Germanidis
authors: Department of Pathology, AHEPA Hospital, Aristotle University of Thessaloniki, School of Medicine, Kyriakidi Str. 1, 54636, Thessaloniki, Greece.
authors: Prodromos
authors: P
authors: Hytiroglou
authors: Centre for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, 11527, Athens, Greece.
authors: Eirini
authors: E
authors: Apostolou
authors: Third Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, 56403, Thessaloniki, Greece.
authors: Themistoklis
authors: T
authors: Vassiliadis
authors: Department of Pathology, Hippokration Hospital, 54635, Thessaloniki, Greece.
authors: Kalliopi
authors: K
authors: Patsiaoura
authors: Centre for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, 11527, Athens, Greece.
authors: Paschalis
authors: P
authors: Sideras
authors: Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Biopolis, 41500, Larissa, Greece.
authors: Anastasios E
authors: AE
authors: Germenis
authors: Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Biopolis, 41500, Larissa, Greece. maspel@med.uth.gr.
authors: Matthaios
authors: M
authors: Speletas
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D002908:Chronic Disease; D005260:Female; D005355:Fibrosis; D006509:Hepatitis B / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012333:RNA, Messenger; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta
keywords: Chronic HBV hepatitis; Non-alcoholic fatty liver disease; SMAD7; TGF-β signaling