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/alpha-smooth muscle actin (alphaSMA) staining revealed that more than 97% of c-Myb-positive cells were alphaSMA-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.
Kitada
T
T
Department of Public Health, Osaka City University Medical School, Osaka, Japan.
Seki
S
S
Nakatani
K
K
Kawada
N
N
Kuroki
T
T
Monna
T
T
D000199:Actins / Q000032:analysis; D000328:Adult; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001706:Biopsy; D015153:Blotting, Western; D002908:Chronic Disease; D005260:Female; D006525:Hepatitis, Viral, Human / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism*
D000199:Actins; D000911:Antibodies, Monoclonal; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators