Thymus cell antigen-1-expressing cells in the oval cell compartment.
Thymus cell antigen-1-expressing cells in the oval cell compartment.
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卵圆细胞室中表达胸腺细胞抗原 1 的细胞。
DOI：
10.1002/hep.23012
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Dabeva,MarianaD
中科院分区：
文献类型：
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作者：
Yovchev,MladenI;Zhang,Jialin;Neufeld,DavidS;Grozdanov,PetarN;Dabeva,MarianaD
在卵圆细胞（OC）介导的肝再生过程中，表达Thy细胞抗原-1（Thy-1）的细胞在肝脏中增殖。我们在正常肝脏、四氯化碳损伤的肝脏和几种OC活化模型中表征了这些细胞。使用逆转录酶聚合酶链反应（RT-PCR）、荧光激活细胞分选（FACS）分离细胞的定量RT-PCR（Q-RT-PCR）以及组织切片和分离细胞的免疫荧光显微镜进行基因表达分析。在正常肝脏中，Thy-1+细胞是一个异质性群体：位于门静脉周围区域的细胞不共表达结蛋白或α平滑肌肌动蛋白（α-SMA）。大多数Thy-1+细胞位于小叶界面和实质中，共表达结蛋白，但不表达α-SMA，即，它们不是常驻肌成纤维细胞。尽管Thy-1+细胞在四氯化碳损伤后适度增殖，但在OC介导的肝再生的所有模型中，它们迅速增殖并显著扩增，并在OC反应消退时从肝脏中消失。活化的Thy-1+细胞不表达OC基因，但它们表达已知在间充质干细胞中表达的基因（CD 105、CD 73、CD 29）、被认为对活化的星状细胞（结蛋白、胶原I-a2、Mmp 2、Mmp 14）和肌成纤维细胞（α-SMA、fibulin-2）具有特异性的基因，以及可影响OC生长的生长因子和细胞因子（Hgf、Tweak、IL-1b、IL-6、IL-15）。活化的玻璃星状细胞不表达Thy-1。从OC活化的肝脏亚克隆Thy-1+细胞产生Thy-1+成纤维细胞和E-钙粘蛋白+间充质细胞群，其逐渐停止Thy-1的表达并开始表达细胞角蛋白。然而，在移植时，这些细胞不分化成肝细胞或胆管细胞。活化的Thy-1+细胞主要产生潜伏性转化生长因子β。结论：OC龛中的Thy-1+细胞是活化的间充质上皮细胞，与常驻星状细胞、肌成纤维细胞和卵圆细胞不同。（肝脏学2009年）
Thymus cell antigen‐1 (Thy‐1)‐expressing cells proliferate in the liver during oval cell (OC)‐mediated liver regeneration. We characterized these cells in normal liver, in carbon tetrachloride‐injured liver, and in several models of OC activation. The gene expression analyses were performed using reverse‐transcriptase polymerase chain reaction (RT‐PCR), quantitative RT‐PCR (Q‐RT‐PCR) of cells isolated by fluorescence‐activated cell sorting (FACS), and by immunofluorescent microscopy of tissue sections and isolated cells. In normal liver, Thy‐1+cells are a heterogeneous population: those located in the periportal region do not coexpress desmin or alpha smooth muscle actin (α‐SMA). The majority of Thy‐1+cells located at the lobular interface and in the parenchyma coexpress desmin but not α‐SMA, i.e., they are not resident myofibroblasts. Although Thy‐1+cells proliferate moderately after carbon tetrachloride injury, in all models of OC‐mediated liver regeneration they proliferate quickly and expand significantly and disappear from the liver when the OC response subsides. Activated Thy‐1+cells do not express OC genes but they express genes known to be expressed in mesenchymal stem cells (CD105, CD73, CD29), genes considered specific for activated stellate cells (desmin, collagen I‐a2, Mmp2, Mmp14) and myofibroblasts (α‐SMA, fibulin‐2), as well as growth factors and cytokines (Hgf, Tweak, IL‐1b, IL‐6, IL‐15) that can affect OC growth. Activatedin vitrostellate cells do not express Thy‐1. Subcloning of Thy‐1+cells from OC‐activated livers yield Thy‐1+fibroblastic cells and a population of E‐cadherin+mesenchymal cells that gradually discontinue expression of Thy‐1 and begin to express cytokeratins. However, upon transplantation these cells do not differentiate into hepatocytes or cholangiocytes. Activated Thy‐1+cells produce predominantly latent transforming growth factor beta.Conclusion:Thy‐1+cells in the OC niche are activated mesenchymal‐epithelial cells that are distinct from resident stellate cells, myofibroblasts, and oval cells. (HEPATOLOGY2009.)