Lv Yinghui, Wang Qizhao, Diao Yong, Xu Ruian
Institute of Molecular Medicine, Huaqiao University 362021, China.
Curr Gene Ther. 2008 Aug;8(4):287-94. doi: 10.2174/156652308785160656.
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.
传统基因疗法已尝试抑制肝纤维化，但潜在的致癌活性可能会阻碍其临床应用。最近，一种用于解决肝纤维化和肝硬化的新主要方法已经开发出来：利用内源性表达基因使肝星状细胞（HSC）失活，这可以介导肝脏的稳态适应。细胞珠蛋白（Cygb）最初是在培养的大鼠HSC中发现的，属于一类新的含血红素蛋白质，称为六配位珠蛋白超家族。这些蛋白质对过氧化氢和脂质氢过氧化物具有过氧化物酶活性。由于Cygb表达的上调可以减轻氧化应激、抑制HSC向肌成纤维细胞样表型的分化并最终阻止肝纤维化的进展，因此人们相当关注在纤维化治疗中使用Cygb的潜在益处。Cygb还被发现是一种候选肿瘤抑制基因，可能为癌症基因治疗提供新的选择。在这篇综述中，我们系统地分析了Cygb作为治疗纤维化、癌症和其他疾病（如糖尿病）的前瞻性基因药物的潜力。同时也综述了Cygb的分子结构、调控和亚细胞定位。
