title: Zinc finger protein A20 protects rats against chronic liver allograft dysfunction.
abstract: OBJECTIVE
  To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats.
  
  
  METHODS
  Allogeneic liver transplantation from DA rats to Lewis rats was performed. Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day (POD) 5. Hepatic overexpression of A20 was achieved by recombinant adenovirus (rAd.)-mediated gene transfer administered intravenously every 10 d starting from POD 10. The recipient rats were injected with physiological saline, rAdEasy-A20 (1 × 10(9) pfu/30 g weight) or rAdEasy (1 × 10(9) pfu/30 g weight) every 10 d through the tail vein for 3 mo starting from POD 10. Liver tissue samples were harvested on POD 30 and POD 60.
  
  
  RESULTS
  Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis. A20 overexpression ameliorated the effects on liver function, attenuated liver allograft fibrosis and prolonged the survival of the recipient rats. Treatment with A20 suppressed hepatic protein production of tumor growth factor (TGF)-β1, interleukin-1β, caspase-8, CD40, CD40L, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin. A20 treatment suppressed liver cell apoptosis and inhibited nuclear factor-κB activation of Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs.
  
  
  CONCLUSIONS
  A20 might prevent chronic liver allograft dysfunction by re-establishing functional homeostasis of KCs, LSECs and HSCs.
authors: Department of Liver and Vascular Surgery, Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors: Jie
authors: J
authors: Yang
authors: Ming-Qing
authors: MQ
authors: Xu
authors: Lu-Nan
authors: LN
authors: Yan
authors: Xiao-Bo
authors: XB
authors: Chen
authors: Jiao
authors: J
authors: Liu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D002908:Chronic Disease; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D055166:Hepatic Stellate Cells / Q000378:metabolism; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000517:prevention & control; D008107:Liver Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse; D016559:Tacrolimus