Expression of large tenascin-C splice variants by hepatic stellate cells/myofibroblasts in chronic hepatitis C
Expression of large tenascin-C splice variants by hepatic stellate cells/myofibroblasts in chronic hepatitis C
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DOI：
10.1016/j.jhep.2006.10.011
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发表时间：
2007-04-01
影响因子：
25.7
通讯作者：
Yoshida, Toshimichi
中科院分区：
文献类型：
--
作者：
El-Karef, Amro;Kaito, Masahiko;Yoshida, Toshimichi
背景/目的：早期研究表明腱生蛋白C（TN-C）参与肝纤维化。在这里，我们研究了TN-C变异体的表达和类型的选择性剪接纤连蛋白III型（FNIII）重复在慢性hepatitis.Methods：使用三种单克隆抗体对TN-C变异体，免疫组化染色，并与慢性丙型肝炎的组织学参数的相关性进行了研究。还确定了细胞来源，并使用分离的大鼠肝星状细胞（HSC）、肝肌成纤维细胞和/或L190细胞测试了变体表达及其类型。大的变异体在正常肝脏中不表达，但在慢性肝炎中表达上调，特别是在界面肝炎和融合性坏死部位，显示染色强度与这些参数之间的相关性比与其他参数或纤维化之间的相关性更强。TN-C沉积与α-平滑肌肌动蛋白阳性细胞（即活化的HSC/肌成纤维细胞）数量的增加密切相关，原位杂交显示细胞中存在TN-C mRNA信号。培养物中活化的HSC和肌成纤维细胞高度表达TN-C的大变体。在L190细胞中，大的变体的测序显示，FNIII重复D和A1/A4，其次是B，优先included.Conclusions：TN-C及其变体产生的HSC/肌成纤维细胞，这表明在肝纤维化的重要作用。(c)2006年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Earlier studies have suggested involvement of tenascin-C (TN-C) in liver fibrosis. Here, we examined expression of TN-C variants and types of alternatively spliced fibronectin-type III (FNIII) repeats in chronic hepatitis.Methods: Using three monoclonal antibodies against TN-C variants, immunohistochemical staining was performed and the correlation with histological parameters of chronic hepatitis C was examined. The cellular source was also determined and variant expression and their types were tested using isolated rat hepatic stellate cells (HSCs), liver myofibroblasts, and/or L190 cells.Results: Large variants were not expressed in normal liver, but were up-regulated in chronic hepatitis, especially at sites of interface hepatitis and confluent necrosis, showing stronger correlations between staining intensity and these than with other parameters or fibrosis. TN-C deposition was closely correlated with increase in the number of alpha-smooth muscle actin-positive cells, i.e. activated HSCs/myofibroblasts, and in situ hybridization showed TN-C mRNA signals in the cells. Activated HSCs and myofibroblasts in culture highly expressed large variants of TN-C. In L190 cells, sequencing of large variants revealed that the FNIII repeats D and A1/A4, followed by B, were preferentially included.Conclusions: TN-C and its variants are produced by HSCs/myofibroblasts, suggesting important roles in liver fibrogenesis. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.