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Functional analysis of differentially expressed genes in hepatic stem cells and the application to the diagnosis of chronic hepatitis and liver cirrhosis.

肝干细胞差异表达基因的功能分析及其在慢性肝炎、肝硬化诊断中的应用

基本信息

批准号：
17590335
负责人：
KANO Junko
金额：
$ 2.24万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

We have demonstrated for the first time that APP and DKK-3 are differentially expressed in adult HSLCs. The expression of APP and DKK-3 in the liver was characteristically higher at a very early fetal stage than in the intermediate or late stage, or in adult liver, and was inversely correlated with the expression of AFP and ALB. Moreover, DKK-3, like AFP, was up-regulated in 7D liver of 80% HM. Both 5^<th> GW fetal liver and 7D liver of 80% HM were shown to be proliferating and to have similar developing histology. Cells expressing DKK-3 were located in the hepatic parenchyma of 5^<th> GW fetal liver, and in the periportal area of normal and regenerating adult liver, suggesting the possible presence of adult HSLCs in the periportal area. These results suggested that DKK-3 was up-regulated in immature and developing liver, and was possibly involved in hepatic differentiation and liver regeneration. Furthermore, to evaluate the relation between DKK-3 expression and hepatic differentiation in hepatoblastomas (HBLs) and hepatocellular carcinomas (HCCs) and the utility of DKK-3 as a diagnostic marker of these hepatic malignant tumors, we analyzed the expression pattern of DKK-3 in primary fourteen HBLs and seventy-two HCCs by in situ hybridization and IHC. Cases expressing DKK-3 were 79% in HBLs and 21% in HCCs. Cases co-expressing DKK-3 and alpha-fetoprotein (AFP) were 57% in HBLs and 10% in HCCs, and cases expressing DKK-3 or AFP were 100% in HBLs and 72% in HCCs. The results support the histological similarity of HBLs to embryonal or fetal liver rather than HCCs, and suggest that DKK-3 is a useful diagnostic marker of HBLs to detect the wide rage of HBLs.

我们首次证明APP和DKK-3在成人HSLC中差异表达。APP和DKK-3在肝脏中的表达特征性地在非常早期的胎儿阶段高于在中期或晚期阶段，或在成人肝脏中，并且与AFP和ALB的表达呈负相关。此外，DKK-3，像AFP，在7 D肝脏中上调80% HM。5^<th>GW胎肝和80% HM的7 D肝脏均显示正在增殖，并且具有相似的发育组织学。表达DKK-3的细胞位于5 μ GW胎肝的肝实质<th>中，以及正常和再生的成人肝的门静脉周围区域中，表明在门静脉周围区域中可能存在成人HSLC。这些结果提示DKK-3在未成熟和发育中的肝脏中表达上调，可能参与了肝脏的分化和再生。此外，为了评价DKK-3表达与肝母细胞瘤（HBL）和肝细胞癌（HCC）中肝分化的关系以及DKK-3作为这些肝脏恶性肿瘤的诊断标志物的实用性，我们通过原位杂交和IHC分析了DKK-3在原发性14例HBL和72例HCC中的表达模式。DKK-3在HBLs中的表达率为79%，在HCC中为21%。DKK-3和AFP共表达者在HBLs中占57%，在HCC中占10%，DKK-3和AFP共表达者在HBLs中占100%，在HCC中占72%。结果支持HBLs与胚胎或胎肝而不是HCC的组织学相似性，并表明DKK-3是HBLs的有用诊断标记物，以检测广泛的HBLs。