Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 21, 2012; 18(27): 3537-3550
Published online Jul 21, 2012. doi: 10.3748/wjg.v18.i27.3537
Zinc finger protein A20 protects rats against chronic liver allograft dysfunction
Jie Yang, Ming-Qing Xu, Lu-Nan Yan, Xiao-Bo Chen, Jiao Liu
Jie Yang, Ming-Qing Xu, Lu-Nan Yan, Xiao-Bo Chen, Jiao Liu, Department of Liver and Vascular Surgery, Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Xu MQ and Yan LN designed the research; Yang J collected the data; Chen XB and Liu J performed statistical analysis; Yang J and Xu MQ wrote the paper.
Supported by The National Natural Science Foundation of China, No. 30872529; the PhD Program Fund of the Ministry of Education of China, No. 20030610078; and the Chinese Postdoctoral Science Foundation, No. 2003033531
Correspondence to: Ming-Qing Xu, MD, PhD, Department of Liver and Vascular Surgery, Liver Transplantation Center, Department of Liver and Vascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. xumingqing0018@163.com
Telephone: +86-28-85422867 Fax: +86-28-85422867
Received: December 7, 2011
Revised: March 3, 2012
Accepted: April 13, 2012
Published online: July 21, 2012
Abstract

AIM: 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 × 109 pfu/30 g weight) or rAdEasy (1 × 109 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.

CONCLUSION: A20 might prevent chronic liver allograft dysfunction by re-establishing functional homeostasis of KCs, LSECs and HSCs.

Keywords: Chronic allograft dysfunction; Liver transplantation; Zinc finger protein A20; Rat