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

Kamrul A.S.M. Huda, Lei Guo, Sanae Haga, Hiroshi Murata, Tetsuya Ogino, Moto Fukai, Takahito Yagi, Hiromi Iwagaki, Noriaki Tanaka, Michitaka Ozaki

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)415-423
Number of pages9
JournalTransplant International
Volume19
Issue number5
DOIs
Publication statusPublished - May 2006

Keywords

  • Ex vivo gene transfer
  • Liver injury
  • Regeneration
  • Signal transducer and activator of transcription-3
  • Small-for-size liver transplantation

ASJC Scopus subject areas

  • Transplantation

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