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

Transplant International : Official Journal of the European Society for Organ Transplantation
Kamrul A S M HudaMichitaka Ozaki

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...Continue Reading

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Citations

Aug 22, 2012·The Journal of Surgical Research·Patricia Aguilar-MeleroPedro López-Cillero
Jan 3, 2008·Transplant International : Official Journal of the European Society for Organ Transplantation·Jun SongXue-Hao Wang
Mar 10, 2010·Transplant International : Official Journal of the European Society for Organ Transplantation·Junjian LiTingbo Liang
Dec 15, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Cleide G da SilvaChristiane Ferran
Jul 8, 2010·Journal of Hepato-biliary-pancreatic Sciences·Masato Fujiyoshi, Michitaka Ozaki
Jul 4, 2013·Journal of Veterinary Science·Hyo-Jung KwonYoung-Suk Won

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