Immunohistochemical characterization of glial fibrillary acidic protein (GFAP)-expressing cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA)
Immunohistochemical characterization of glial fibrillary acidic protein (GFAP)-expressing cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA)
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DOI：
10.1016/j.etp.2014.09.008
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Yamate, Jyoji
中科院分区：
文献类型：
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作者：
Tennakoon, Anusha Hemamali;Izawa, Takeshi;Yamate, Jyoji
肝星状细胞是肝脏中主要的纤维化细胞类型，已知其表达星形胶质细胞标志物胶质细胞酸性蛋白（GFAP）。然而，GFAP表达细胞在肝纤维化中的确切作用仍有待阐明。在这项研究中，GFAP表达细胞的细胞特性进行了研究，在大鼠肝硬化模型。对6周龄雄性F344大鼠腹膜内注射硫代乙酰胺（100 mg/kg BW，每周两次），并在首次注射后第5、10、15、20和25周进行检查。表达GFAP的肌成纤维细胞的出现在第15周达到峰值，与纤维化进展相关。大多数表达GFAP的肌成纤维细胞共表达波形蛋白、结蛋白和α-平滑肌肌动蛋白。部分GFAP阳性肌成纤维细胞共表达神经干细胞标志物nestin，少数共表达间充质干细胞标志物A3和未成熟间充质细胞标志物Thy-1。少数表达GFAP的细胞同时经历有丝分裂和凋亡。这些结果表明，有一个动态的参与GFAP表达肌成纤维细胞在大鼠肝硬化，他们主要来自肝星状细胞，部分来自干细胞谱系的细胞。这些发现，这是第一次详细显示，将有助于了解GFAP表达的肌成纤维细胞在化学诱导的肝硬化的发病机制中的作用。(C)2014 Elsevier GmbH. All rights reserved.
Hepatic stellate cells, the principal fibrogenic cell type in the liver, are known to express the astrocyte marker glial fibrillary acidic protein (GFAP). However, the exact role of GFAP-expressing cells in liver fibrosis remains to be elucidated. In this study, cellular properties of GFAP-expressing cells were investigated in a rat model of liver cirrhosis. Six-week-old male F344 rats were injected intraperitoneally with thioacetamide (100 mg/kg BW, twice a week) and examined at post first injection weeks 5, 10, 15, 20 and 25. Appearance of GFAP-expressing myofibroblasts peaked at week 15, associated with fibrosis progression. The majority of GFAP-expressing myofibroblasts co-expressed vimentin, desmin and alpha-smooth muscle actin. Some GFAP-positive myofibroblasts co-expressed nestin (neural stem cell marker), while a few co-expressed A3 (mesenchymal stem cell marker) and Thy-1 (immature mesenchymal cell marker). A few GFAP expressing cells underwent both mitosis and apoptosis. These results indicate that there is a dynamic participation of GFAP-expressing myofibroblasts in rat liver cirrhosis, and that they are mainly derived from hepatic stellate cells, and partly from cells in the stem cell lineage. These findings, which were shown for the first time in detail, would be useful to understand the role of GFAP-expressing myofibroblasts in the pathogenesis of chemically induced liver cirrhosis. (C) 2014 Elsevier GmbH. All rights reserved.