Analysis of epithelial-mesenchymal transition markers in the histogenesis of hepatic progenitor cell in HBV-related liver diseases.
Analysis of epithelial-mesenchymal transition markers in the histogenesis of hepatic progenitor cell in HBV-related liver diseases.
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乙型肝炎相关肝病肝祖细胞组织发生中的上皮-间质转化标志物分析。
DOI：
10.1186/s13000-016-0587-y
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发表时间：
2016-11-24
影响因子：
2.6
通讯作者：
Deng H
中科院分区：
文献类型：
--
作者：
Xu W;Wang NR;Wang HF;Feng Q;Deng J;Gong ZQ;Sun J;Lou XL;Yu XF;Zhou L;Hu JP;Huang XF;Qi XQ;Deng YJ;Gong R;Guo Y;Wang MM;Xiao JC;Deng H
肝祖细胞（HPC）的起源和异质性仍不清楚。本研究旨在探讨上皮间质转化（EMT）在 HPC 组织发生中的作用。采用双重免疫荧光标记技术对来自 HBV 相关肝炎和肝硬化患者的手术肝脏标本进行研究，以检测与 HPC 和 EMT 相关的抗原。通过激光捕获显微切割分离后，对导管反应进行定量逆转录 PCR。进行电子显微镜检查以寻找 EMT 的超微结构证据。 EpCAM 阳性 HPC 的数量与疾病严重程度成正比。 HPCs S100A4 表达首先出现在轻型肝炎中，在中度肝炎中显着升高，而在重型肝炎和肝硬化中降低。 MMP-2、Twist 和 Snail 的水平增加与 HPC 的数量成正比。肝硬化中邻近汇管束的一些肝细胞显示 MMP-2 阳性。尽管CK7和E-钙粘蛋白水平在轻度和中度肝炎中下降，但HPCs在重度肝炎和肝硬化中重新表达这两者。然而，HPC 既不表达波形蛋白也不表达 αSMA。 EpCAM 和 EMT 相关标记物的相对 mRNA 表达水平支持免疫组织化学结果。电子显微镜检查表明 HPC、胆管细胞和中间肝细胞样细胞之间存在细胞间连接。我们为 EMT 参与 HBV 相关肝脏疾病中胆管细胞 HPC 的组织发生提供了初步证据。 HPCs可能会重新转分化为肝细胞，并且分化方向至少部分取决于HPCs与周围微环境之间的相互作用，尤其是HBV感染引起的非消退性炎症。
The origin and heterogeneity of hepatic progenitor cells (HPCs) remain unclear. This study aimed to investigate the involvement of epithelial-mesenchymal transition (EMT) in the histogenesis of HPCs. Surgical liver specimens from patients with HBV-related hepatitis and cirrhosis were investigated with double immunofluorescence labeling to detect antigens associated with HPCs and EMT. Ductular reactions were subjected to quantitative reverse transcription PCR following isolation by laser capture microdissection. Electron microscopic examination was performed to find an ultrastructural evidence of EMT. The number of EpCAM-positive HPCs was proportional to the disease severity. The S100A4 expression of HPCs was firstly observed in mild hepatitis and increased significantly in moderate hepatitis, but decreased in severe hepatitis and cirrhosis. The levels of MMP-2, Twist, and Snail increased in direct proportion to the number of HPCs. Some hepatocytes adjacent to portal tracts in cirrhosis showed positivity for MMP-2. Although CK7 and E-cadherin levels decreased in mild and moderate hepatitis, HPCs re-expressed both of them in severe hepatitis and cirrhosis. However, HPCs expressed neither vimentin nor αSMA. The relative mRNA expression levels of EpCAM and EMT-associated markers supported immunohistochemical results. Electron microscopic examination demonstrated the existence of intercellular junctions among HPCs, cholangiocytes, and intermediate hepatocyte-like cells. We provided preliminary evidence for the involvement of EMT in the histogenesis of HPCs from cholangiocytes in HBV-related liver diseases. HPCs may re-transdifferentiate into hepatocytes, and the differentiation direction depends, at least in part, on interactions between HPCs and the surrounding microenvironment, especially the non-resolving inflammation caused by HBV infection.
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影响因子：
64.8
作者：
CEPEK, KL;SHAW, SK;BRENNER, MB
通讯作者：
BRENNER, MB
影响因子：
1.5
作者：
Means, Anna L.;Xu, Yanwen;Gu, Guoqiang
通讯作者：
Gu, Guoqiang
影响因子：
15.9
作者：
Omenetti, Alessia;Porrello, Alessandro;Diehl, Anna Mae
通讯作者：
Diehl, Anna Mae
影响因子：
64.8
作者：
Radisky, DC;Levy, DD;Bissell, MJ
通讯作者：
Bissell, MJ
影响因子：
13.5
作者：
Bedossa, P;Poynard, T
通讯作者：
Poynard, T