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 : official journal of the European Society for Organ Transplantation
Volume19
Issue number5
DOIs
Publication statusPublished - May 2006

Fingerprint

STAT3 Transcription Factor
Regeneration
Transplants
Liver Regeneration
Liver
Wounds and Injuries
Genes
DNA
Electrophoretic Mobility Shift Assay
Aspartate Aminotransferases
Protein C
Serum
Alanine Transaminase
Bilirubin
Adenoviridae
Biochemistry
Liver Transplantation
Albumins
Transcription Factors
Western Blotting

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

Cite this

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

In: Transplant international : official journal of the European Society for Organ Transplantation, Vol. 19, No. 5, 05.2006, p. 415-423.

Research output: Contribution to journalArticle

Huda, Kamrul A S M ; Guo, Lei ; Haga, Sanae ; Murata, Hiroshi ; Ogino, Tetsuya ; Fukai, Moto ; Yagi, Takahito ; Iwagaki, Hiromi ; Tanaka, Noriaki ; Ozaki, Michitaka. / 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. In: Transplant international : official journal of the European Society for Organ Transplantation. 2006 ; Vol. 19, No. 5. pp. 415-423.
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