Current Gene Therapy

Ignacio Anegon
Director INSERM UMR 1064-Center for Research in Transplantation and Immunology
CHU de Nantes. 30, boulevard
Nantes
France

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Cytoglobin:A Novel Potential Gene Medicine for Fibrosis and Cancer Therapy

Author(s): Yinghui Lv, Qizhao Wang, Yong Diao, Ruian Xu.

Abstract:

Attempts have been made by conventional gene therapy to suppress hepatic fibrogenesis, but potential oncogenic activity may prevent its clinical use. Recently, a novel major approach has been developed for resolution of liver fibrosis and cirrhosis: inactivation of hepatic stellate cells (HSC) using the endogenous expressing gene, which could mediate the homeostatic adaptation of liver. Cytoglobin (Cygb), originally identified in cultured rat HSC, is in a new class of heme containing proteins known as the hexacoordinate globin superfamily. These proteins exhibit peroxidase activity against hydrogen peroxides and lipid hydroperoxides. Considerable attention has been focused on the potential benefits of use of Cygb in fibrosis therapy, as up-regulation of Cygb expression could reduce oxidant stress, suppress HSC differentiation to a myofibroblast-like phenotype and eventually prevent the progress of liver fibrosis. Cygb has also been found to be a candidate tumor suppressor gene that might provide a new option for cancer gene therapy. In this review we systematically analyze the potential of Cygb as a prospective gene medicine for curing fibrosis, cancer, and other diseases such as diabetes. The molecular structure, regulation and subcellular location of Cygb are reviewed as well.

Keywords: Hexacoordination, oxidative stress, hypoxia, up-regulation, stellate cell, tumor suppressor, hypermethylated, gene therapy

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Article Details

VOLUME: 8
ISSUE: 4
Year: 2008
Page: [287 - 294]
Pages: 8
DOI: 10.2174/156652308785160656
Price: $58