Localization and expression pattern of cytoglobin in carbon tetrachloride-induced liver fibrosis.

Cytoglobin (Cygb) is a recently discovered hexacoordinate globin protein with a yet undefined function. It was found to be up-regulated in toxin-induced liver fibrosis and during hypoxic conditions [Fago, A., Hundahl, C., Malte, H., Weber, R.E., 2004. Functional properties of neuroglobin and cytoglobin. Insights into the ancestral physiological roles of globins. IUBMB Life 56, 689-696; Fordel, E., Thijs, L., Martinet, W., Schrijvers, D., Moens, L., Dewilde, S., 2007. Anoxia or oxygen and glucose deprivation in SH-SY5Y cells: a step closer to the unraveling of neuroglobin and cytoglobin functions. Gene 398, 114-122; Guo, X., Philipsen, S., Tan-Un, K.C., 2007. Study of the hypoxia-dependent regulation of human CYGB gene. Biochem. Biophys. Res. Commun. 364, 145-150; Li, D., Chen, X.Q., Li, W.J., Yang, Y.H., Wang, J.Z., Yu, A.C., 2007. Cytoglobin up-regulated by hydrogen peroxide plays a protective role in oxidative stress. Neurochem. Res. 32, 1375-1380]. Cygb is expressed ubiquitously in most tissues but its subcellular localization in certain cell types (e.g. hepatocytes) is still controversial. In this study we investigated the localization of Cygb protein in mouse tissues, its expression pattern in response to carbon tetrachloride (CCl(4)) challenge and that during CCl(4)-induced liver fibrosis in order to delineate the functional property of Cygb. We found that it is expressed in fibroblasts in various organs and in the hepatic stellate cells. Cygb mRNA expression is up-regulated by more than 3.5-fold 24h after administration of CCl(4). At 48h post-administration, the expression of procollagen I alpha 1 mRNA was increased by over 7.6-fold. The increase in collagen expression after CCl(4) insult was also evident at the protein level. We found that the number of Cygb-expressing cells increased through the development of CCl(4)-induced liver fibrosis. It may be possible that Cygb is an early biomarker for liver fibrosis.