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Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model

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Abstract:

Summary

Signal transducer and activator of transcription-3 (STAT3) is one of the most important transcription factors for liver regeneration. This study was designed to examine the effects of constitutively activated STAT3 (STAT3-C) on post-transplant liver injury and regeneration in a rat 20% partial liver transplant (PLTx) model by ex vivo adenoviral gene transfer. Adenovirus encoding the STAT3-C gene was introduced intraportally into liver grafts and clamped for 30 min during cold preservation. After orthotopic PLTx, liver graft/body weights and serum biochemistry were monitored, and both a histological study and DNA binding assay were performed. STAT3-C protein expression and its binding to DNA in the liver graft were confirmed by Western blotting and electrophoretic mobility shift assay (EMSA), respectively. This treatment modality promoted post-Tx liver regeneration effectively and rapidly. The serum levels of alanine aminotransferase/aspartate aminotransferase (AST/ALT) and bilirubin decreased in rats with STAT3-C. However, albumin (a marker of liver function) did not. Ex vivo gene transfer of STAT3-C to liver grafts reduced post-Tx injury and promoted liver regeneration. Thus, the activation of STAT3 in the liver graft may be a potentially effective clinical strategy for improving the outcome of small-for-size liver transplantation.

Keywords: ex vivo gene transfer; liver injury; regeneration; signal transducer and activator of transcription-3; small-for-size liver transplantation

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1432-2277.2006.00285.x

Affiliations: 1: Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, Shikata, Okayama, Japan 2: Department of Artificial Organ and Transplantation Surgery, University of Tokyo School of Medicine, Hongo, Tokyo, Japan 3: Department of Surgery, Division of Organ Transplantation and Regenerative Medicine, Hokkaido University Graduate School of Medicine, School of Medicine, Kita-ku, Sapporo, Japan 4: Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Shikata, Okayama, Japan

Publication date: May 1, 2006

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