Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver
Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver
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DOI：
10.1038/labinvest.2013.135
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发表时间：
2014-02-01
影响因子：
5
通讯作者：
Kawada, Norifumi
中科院分区：
文献类型：
--
作者：
Motoyama, Hiroyuki;Komiya, Tohru;Kawada, Norifumi
细胞珠蛋白（CYGB）广泛表达于许多器官成纤维细胞的细胞质中，包括肝星状细胞。到目前为止，还没有特异性的标记物来区分人类肝脏中的星状细胞和肌成纤维细胞。为了研究CYGB是否可以用于区分正常和纤维化人类肝脏中的肝星状细胞和肌成纤维细胞，通过肝活检获得了由丙型肝炎病毒（HCV）感染损伤的人类肝脏组织和在纤维化的不同阶段。使用抗CYGB、细胞视黄醇结合蛋白-1（CRBP-1）、α-平滑肌肌动蛋白（α-SMA）、胸腺细胞分化抗原1（Thy-1）和纤蛋白-2（FBLN 2）的抗体对肝组织的组织切片进行免疫组织化学。CYGB和CRBP-1阳性细胞计数周围的纤维化汇管区的组织切片的样品。在培养的小鼠星状细胞中检测了上述几种蛋白质的表达。静止的星状细胞，但不门静脉肌成纤维细胞，表达CYGB和CRBP-1在正常肝脏。在纤维化和硬化的肝脏中，星状细胞表达CYGB和α-SMA，而门静脉周围的肌成纤维细胞表达α-SMA、Thy-1和FBLN 2，但不表达CYGB。纤维化阶段的发展与天狼星红染色、α-SMA阳性和Thy-1阳性区域的增加呈正相关，而CYGB和CRBP-1阳性细胞的数量随着纤维化的发展而减少。原代培养的小鼠星状细胞在第1天表达细胞质CYGB，而它们在第4天开始在细胞边缘表达α-SMA。Thy-1在整个培养过程中均未检测到。在人类肝组织中，静止的星状细胞是CYGB阳性的。当被激活时，它们也变成a-SMA阳性;然而，它们对Thy-1和FBLN 2呈阴性。因此，CYGB是一个有用的标志物，它区分星状细胞从门静脉肌成纤维细胞在受损的人肝脏。
Cytoglobin (CYGB) is ubiquitously expressed in the cytoplasm of fibroblastic cells in many organs, including hepatic stellate cells. As yet, there is no specific marker with which to distinguish stellate cells from myofibroblasts in the human liver. To investigate whether CYGB can be utilized to distinguish hepatic stellate cells from myofibroblasts in normal and fibrotic human liver, human liver tissues damaged by infection with hepatitis C virus (HCV) and at different stages of fibrosis were obtained by liver biopsy. Immunohistochemistry was performed on histological sections of liver tissues using antibodies against CYGB, cellular retinol-binding protein-1 (CRBP-1), alpha-smooth muscle actin (alpha-SMA), thymocyte differentiation antigen 1 (Thy-1), and fibulin-2 (FBLN2). CYGB- and CRBP-1-positive cells were counted around fibrotic portal tracts in histological sections of the samples. The expression of several of the proteins listed above was examined in cultured mouse stellate cells. Quiescent stellate cells, but not portal myofibroblasts, expressed both CYGB and CRBP-1 in normal livers. In fibrotic and cirrhotic livers, stellate cells expressed both CYGB and a-SMA, whereas myofibroblasts around the portal vein expressed a-SMA, Thy-1, and FBLN2, but not CYGB. Development of the fibrotic stage was positively correlated with increases in Sirius red-stained, alpha-SMA-positive, and Thy-1-positive areas, whereas the number of CYGB- and CRBP-1-positive cells decreased with fibrosis development. Primary cultured mouse stellate cells expressed cytoplasmic CYGB at day 1, whereas they began to express a-SMA at the cellular margins at day 4. Thy-1 was undetectable throughout the culture period. In human liver tissues, quiescent stellate cells are CYGB positive. When activated, they also become a-SMA positive; however, they are negative for Thy-1 and FBLN2. Thus, CYGB is a useful marker with which to distinguish stellate cells from portal myofibroblasts in the damaged human liver.