Abstract

Background: Cholestasis occurs in a wide variety of human liver diseases, and hepatocellular injury is an invariant feature of cholestasis, causing liver dysfunction and inflammation, promoting fibrogenesis, and ultimately leading to liver failure. Insulin-like growth factor 1 (IGF1) acts in an autocrine and paracrine manner to promote glucose utilization, using phosphatidylinositol 3 kinase (PI3 K)/Akt, the downstream glycogen synthase kinase 3β (GSK3β), and anti-apoptotic pathways. This study investigated whether gene transfer of IGF1 could attenuate hepatocellular injury after bile duct ligation in rats. Materials and Methods: Experiments were performed in 80 male Sprague-Dawley rats. Thirty minutes after bile duct ligation, hydrodynamics-based gene transfection with IGF1 plasmid via rapid tail vein injection. The rats were randomly divided into the following four groups: sham operated; BDL treated with pCMV-IGF1 gene; BDL treated with vehicle for pCMV-LacZ gene; and BDL only. Results: IGF1 expression in liver after a single administration of IGF-1 plasmid was demonstrated. Liver function index, including serum alanine aminotransferase and aspartate aminotransferase, were significantly reduced in IGF1 gene transfer rats. We determined the mechanism of IGF1 gene transfer after BDL in terms of activation of Akt, inhibition of GSK3β, and blockage of caspase-9 cleavage. Furthermore, hepatocyte stellate cell activation was markedly inhibited in IGF1 gene-treated rats. Apoptosis was significantly attenuated by IGF1 gene therapy. Conclusions: This study demonstrated that gene transfer of IGF1 could attenuate hepatocellular apoptosis and injury after bile duct ligation in rats.

Original languageEnglish
Pages (from-to)237-244
Number of pages8
JournalJournal of Surgical Research
Volume167
Issue number2
DOIs
Publication statusPublished - May 15 2011

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Somatomedins
Bile Ducts
Ligation
Apoptosis
Genes
Glycogen Synthase Kinase 3
Cholestasis
Liver Diseases
Wounds and Injuries
Plasmids
Phosphatidylinositol 3-Kinase
Lac Operon
Caspase 9
Liver
Liver Failure
Hydrodynamics
Aspartate Aminotransferases
Alanine Transaminase
Insulin-Like Growth Factor I
Genetic Therapy

Keywords

  • Akt
  • apoptosis
  • cholestasis
  • gene transfer
  • insulin-like growth factor 1

ASJC Scopus subject areas

  • Surgery

Cite this

Gene transfer of IGF1 attenuates hepatocellular apoptosis after bile duct ligation. / Pi-Chieh Wang, Kenneth; Lee, Liang Ming; Lin, Tien Jen; Sheen-Chen, Shyr Ming; Lin, Jia Wei; Chiu, Wen Ta; Wang, Chien Che; Hung, Kuo Sheng.

In: Journal of Surgical Research, Vol. 167, No. 2, 15.05.2011, p. 237-244.

Research output: Contribution to journalArticle

Pi-Chieh Wang, Kenneth ; Lee, Liang Ming ; Lin, Tien Jen ; Sheen-Chen, Shyr Ming ; Lin, Jia Wei ; Chiu, Wen Ta ; Wang, Chien Che ; Hung, Kuo Sheng. / Gene transfer of IGF1 attenuates hepatocellular apoptosis after bile duct ligation. In: Journal of Surgical Research. 2011 ; Vol. 167, No. 2. pp. 237-244.
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abstract = "Background: Cholestasis occurs in a wide variety of human liver diseases, and hepatocellular injury is an invariant feature of cholestasis, causing liver dysfunction and inflammation, promoting fibrogenesis, and ultimately leading to liver failure. Insulin-like growth factor 1 (IGF1) acts in an autocrine and paracrine manner to promote glucose utilization, using phosphatidylinositol 3 kinase (PI3 K)/Akt, the downstream glycogen synthase kinase 3β (GSK3β), and anti-apoptotic pathways. This study investigated whether gene transfer of IGF1 could attenuate hepatocellular injury after bile duct ligation in rats. Materials and Methods: Experiments were performed in 80 male Sprague-Dawley rats. Thirty minutes after bile duct ligation, hydrodynamics-based gene transfection with IGF1 plasmid via rapid tail vein injection. The rats were randomly divided into the following four groups: sham operated; BDL treated with pCMV-IGF1 gene; BDL treated with vehicle for pCMV-LacZ gene; and BDL only. Results: IGF1 expression in liver after a single administration of IGF-1 plasmid was demonstrated. Liver function index, including serum alanine aminotransferase and aspartate aminotransferase, were significantly reduced in IGF1 gene transfer rats. We determined the mechanism of IGF1 gene transfer after BDL in terms of activation of Akt, inhibition of GSK3β, and blockage of caspase-9 cleavage. Furthermore, hepatocyte stellate cell activation was markedly inhibited in IGF1 gene-treated rats. Apoptosis was significantly attenuated by IGF1 gene therapy. Conclusions: This study demonstrated that gene transfer of IGF1 could attenuate hepatocellular apoptosis and injury after bile duct ligation in rats.",
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AU - Pi-Chieh Wang, Kenneth

AU - Lee, Liang Ming

AU - Lin, Tien Jen

AU - Sheen-Chen, Shyr Ming

AU - Lin, Jia Wei

AU - Chiu, Wen Ta

AU - Wang, Chien Che

AU - Hung, Kuo Sheng

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N2 - Background: Cholestasis occurs in a wide variety of human liver diseases, and hepatocellular injury is an invariant feature of cholestasis, causing liver dysfunction and inflammation, promoting fibrogenesis, and ultimately leading to liver failure. Insulin-like growth factor 1 (IGF1) acts in an autocrine and paracrine manner to promote glucose utilization, using phosphatidylinositol 3 kinase (PI3 K)/Akt, the downstream glycogen synthase kinase 3β (GSK3β), and anti-apoptotic pathways. This study investigated whether gene transfer of IGF1 could attenuate hepatocellular injury after bile duct ligation in rats. Materials and Methods: Experiments were performed in 80 male Sprague-Dawley rats. Thirty minutes after bile duct ligation, hydrodynamics-based gene transfection with IGF1 plasmid via rapid tail vein injection. The rats were randomly divided into the following four groups: sham operated; BDL treated with pCMV-IGF1 gene; BDL treated with vehicle for pCMV-LacZ gene; and BDL only. Results: IGF1 expression in liver after a single administration of IGF-1 plasmid was demonstrated. Liver function index, including serum alanine aminotransferase and aspartate aminotransferase, were significantly reduced in IGF1 gene transfer rats. We determined the mechanism of IGF1 gene transfer after BDL in terms of activation of Akt, inhibition of GSK3β, and blockage of caspase-9 cleavage. Furthermore, hepatocyte stellate cell activation was markedly inhibited in IGF1 gene-treated rats. Apoptosis was significantly attenuated by IGF1 gene therapy. Conclusions: This study demonstrated that gene transfer of IGF1 could attenuate hepatocellular apoptosis and injury after bile duct ligation in rats.

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