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Digestive Diseases and Sciences

Erschienen in:

01.04.2012 | Original Article

Gene Transfer of c-met Confers Protection Against d-Galactosamine/Lipopolysaccharide-Induced Acute Liver Failure

verfasst von: Chuanlong Zhu, Yuwen Li, Wenting Li, Quan Wu, Rentao Gao

Erschienen in: Digestive Diseases and Sciences | Ausgabe 4/2012

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Abstract

Background

Acute liver failure (ALF) is characterized by impaired regeneration of hepatocytes, partially resulting from the defective signaling between elevated levels of hepatocyte growth factor (HGF) and the downregulation of its receptor, c-met.

Aims

In this study, we assess the therapeutic efficacy of in vivo c-met gene transfer in ALF.

Methods

We established a d-galactosamine/lipopolysaccharide (d-GalN/LPS)-induced ALF model in rats. The levels of HGF and c-met in d-GalN/LPS rats were compared with vehicle-injected rats and those undergoing liver regeneration following partial hepatectomy (PH). To deliver c-met in vivo, pcDNA-c-met was constructed and transfected into the rat liver via hydrodynamic injection. Control rats were transfected with the pcDNA3.1 plasmid. The expressions of c-met in different tissues were examined by immunohistochemistry. Hepatocyte proliferation and apoptosis were determined by PCNA staining and TUNEL assay, respectively. The survival of rats in the control and c-met-expressing rats was compared by Kaplan–Meier analysis.

Results

Compared with control rats, d-GalN/LPS or PH -treated rats had significantly higher levels of HGF (P < 0.01). d-GalN/LPS also led to significantly lower c-met expression in the liver (P < 0.01) than PH. The in vivo c-met gene transfer led to its specific expression on hepatocytes, which was accompanied by the enhancement of hepatocyte proliferation, a reduction in apoptosis, as well as significant improvement in overall survival (P < 0.01).

Conclusions

This study provides the initial evidence that c-met may serve as a novel target for gene therapy, and may be of clinical benefit in the treatment of patients with ALF.

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Titel: Gene Transfer of c-met Confers Protection Against d-Galactosamine/Lipopolysaccharide-Induced Acute Liver Failure
verfasst von: Chuanlong Zhu
Yuwen Li
Wenting Li
Quan Wu
Rentao Gao
Publikationsdatum: 01.04.2012
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 4/2012
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-012-2052-4

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Abstract

Background

Aims

Methods

Results

Conclusions

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