Xu Ruian, Harrison Phillip M, Chen Miao, Li Linyan, Tsui Tung-yu, Fung Peter C W, Cheung Pik-to, Wang Guangji, Li Hua, Diao Yong, Krissansen Geoffrey W, Xu Sue, Farzaneh Farzin
Institute of Molecular Medicine, Huaqiao University, Fujian, China.
Mol Ther. 2006 Jun;13(6):1093-100. doi: 10.1016/j.ymthe.2005.11.027. Epub 2006 Apr 3.
Cytoglobin (Cygb), a member of the hexacoordinate globin superfamily (hxHb), is expressed in fibroblasts from a broad range of tissues. The physiological functions of hxHb are still unclear, but biochemical studies reveal that they can scavenge toxic species, such as nitric oxide, peroxynitrite, and hydrogen peroxide. We demonstrate that the overexpression of Cygb in rat hepatic stellate cells, both in vitro and in vivo, protects against oxidative stress, inhibiting their differentiation into a myofibroblast-like phenotype. Accordingly, the overexpression of Cygb reduces extracellular matrix deposition in both toxic and cholestatic models of liver injury. The overexpression of Cygb also promotes recovery from previously initiated damage-induced fibrogenesis. By inhibiting free radical-induced activation of hepatic stellate cells, Cygb plays an important role in controlling tissue fibrosis. Therefore, the normal upregulation of Cygb during tissue injury has a homeostatic effect, inhibiting free radical-induced fibroblast activation and tissue fibrosis.
细胞珠蛋白（Cygb）是六配位珠蛋白超家族（hxHb）的成员之一，在多种组织的成纤维细胞中表达。hxHb的生理功能尚不清楚，但生化研究表明，它们可以清除有毒物质，如一氧化氮、过氧亚硝酸盐和过氧化氢。我们证明，无论是在体外还是在体内，大鼠肝星状细胞中Cygb的过表达都能抵御氧化应激，抑制它们向肌成纤维细胞样表型的分化。因此，在肝损伤的毒性和胆汁淤积模型中，Cygb的过表达都会减少细胞外基质的沉积。Cygb的过表达还能促进先前引发的损伤诱导纤维化的恢复。通过抑制自由基诱导的肝星状细胞激活，Cygb在控制组织纤维化中发挥重要作用。因此，组织损伤期间Cygb的正常上调具有稳态效应，可抑制自由基诱导的成纤维细胞激活和组织纤维化。
