Hepatic expression of c‐Myb in chronic human liver disease

C‐Myb is a sequence‐specific DNA binding protein that regulates the expression of genes involved in cell proliferation and differentiation. The present study was designed to elucidate the role of c‐Myb in the pathogenesis of chronic liver disease by an immunohistochemical approach. In normal (control) livers, few or no hepatic cells were positive for c‐Myb. In livers from patients with chronic viral hepatitis, positive staining for c‐Myb was found not only in spindle‐shaped mesenchymal cells in expanded portal areas, but also in perisinusoidal cells (PSCs) within liver lobules. In cirrhotic livers, a few PSCs within lobules were positive for c‐Myb, while no staining was seen in fibrous septa. Immunoelectron microscopy revealed that c‐Myb‐positive PSCs displayed morphological features of hepatic stellate cells. Other sinusoidal lining cells including Kupffer cells and sinusoidal endothelial cells, as well as hepatocytes, were all negative for c‐Myb. Dual c‐Myb/α‐smooth muscle actin (αSMA) staining revealed that more than 97% of c‐Myb‐positive cells were αSMA‐positive. Moreover, dual c‐Myb/proliferating cell nuclear antigen (PCNA) staining showed that approximately 70% of c‐Myb‐positive cells also expressed PCNA. The labeling index (LI) (number of c‐Myb‐positive cells/0.1 mm2) significantly correlated with serum transaminase concentrations and increased in parallel with the disease activity. However, the LI showed no correlation with the degree of fibrosis. These results suggest that c‐Myb may be involved in stellate cell activation and proliferation in chronically diseased human livers, and that the level of c‐Myb expression is associated with the activity of chronic hepatitis.

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