Kitada T, Seki S, Nakatani K, Kawada N, Kuroki T, Monna T
Department of Public Health, Osaka City University Medical School, Osaka, Japan.
Hepatology. 1997 Dec;26(6):1506-12. doi: 10.1053/jhep.1997.v26.pm0009397991.
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.
C-Myb是一种序列特异性DNA结合蛋白，可调节参与细胞增殖和分化的基因的表达。本研究旨在通过免疫组织化学方法阐明c-Myb在慢性肝病发病机制中的作用。在正常（对照）肝脏中，很少或没有肝细胞c-Myb呈阳性。在慢性病毒性肝炎患者的肝脏中，不仅在扩大的门管区的梭形间充质细胞中发现c-Myb阳性染色，而且在肝小叶内的窦周细胞（PSC）中也发现了阳性染色。在肝硬化肝脏中，小叶内的少数PSC对c-Myb呈阳性，而在纤维间隔中未观察到染色。免疫电子显微镜显示，c-Myb阳性的PSC表现出肝星状细胞的形态特征。包括库普弗细胞和窦内皮细胞在内的其他窦内衬细胞以及肝细胞，c-Myb均为阴性。c-Myb/α-平滑肌肌动蛋白（αSMA）双重染色显示，超过97%的c-Myb阳性细胞αSMA呈阳性。此外，c-Myb/增殖细胞核抗原（PCNA）双重染色显示，约70%的c-Myb阳性细胞也表达PCNA。标记指数（LI）（c-Myb阳性细胞数/0.1mm2）与血清转氨酶浓度显著相关，并与疾病活动度平行增加。然而，LI与纤维化程度无关。这些结果表明，c-Myb可能参与了慢性病变人类肝脏中星状细胞的激活和增殖，并且c-Myb的表达水平与慢性肝炎的活动度相关。
