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
Current Gene Therapy
Title: Cytoglobin:A Novel Potential Gene Medicine for Fibrosis and Cancer Therapy
Volume: 8 Issue: 4
Author(s): Yinghui Lv, Qizhao Wang, Yong Diao and Ruian Xu
Affiliation:
Keywords: Hexacoordination, oxidative stress, hypoxia, up-regulation, stellate cell, tumor suppressor, hypermethylated, gene therapy
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.
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Cite this article as:
Lv Yinghui, Wang Qizhao, Diao Yong and Xu Ruian, Cytoglobin:A Novel Potential Gene Medicine for Fibrosis and Cancer Therapy, Current Gene Therapy 2008; 8 (4) . https://dx.doi.org/10.2174/156652308785160656
DOI https://dx.doi.org/10.2174/156652308785160656 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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