Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis

Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis
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DOI:
10.1038/labinvest.3700013
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发表时间:
2004-01-01
影响因子:
5
通讯作者:
Yoshizato, K
Yoshizato, K
中科院分区:
医学2区
文献类型:
--
作者:
Nakatani, K;Okuyama, H;Yoshizato, K

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细胞珠蛋白/星状细胞激活相关蛋白(Cygb/STAP)是近年来在大鼠肝星状细胞蛋白质组研究中发现的一类新的六配位珠蛋白超家族。与血红蛋白、肌红蛋白和神经红蛋白不同,Cygb/STAP在几个器官中普遍表达,尽管其详细的定位尚未阐明。免疫组织化学和免疫电子显微镜显示,Cygb/STAP独特地定位于内脏器官的成纤维细胞样细胞,即维生素A储存细胞谱系,但既不存在于上皮细胞、内皮细胞、肌肉细胞、血细胞、巨噬细胞,也不存在于真皮成纤维细胞中。Cygb/STAP的表达在胰腺和肾脏的纤维化病变中上调,其中已知活化的成纤维细胞样细胞或肌成纤维细胞的数量增加。在培养的肝星状细胞中,Cygb/STAP的表达增加了刺激血清,血小板衍生生长因子-BB,和转化生长因子-β 1。Cygb/STAP在NIH 3 T3细胞中的过表达可导致细胞迁移能力减弱,胶原α 1(I)mRNA表达增加。这些结果表明,Cygb/STAP是一种独特的定位于内脏成纤维细胞系的组织珠蛋白,并可能在器官纤维化疾病中发挥作用。
Cytoglobin/stellate cell activation-associated protein (Cygb/STAP) consists of a new class of hexacoordinate globin superfamily, which was recently discovered by a proteome analysis on the rat hepatic stellate cells. Unlike haemoglobin, myoglobin, and neuroglobin, Cygb/STAP is ubiquitously expressed in several organs, although its detailed localization has not been clarified. Immunohistochemistry and immunoelectron microscopy revealed that Cygb/STAP is uniquely localized in fibroblast-like cells in splanchnic organs, namely the vitamin A-storing cell lineage, but neither in epithelial cells, endothelial cells, muscle cells, blood cells, macrophages, nor dermal fibroblasts. The expression of Cygb/STAP was upregulated in fibrotic lesions of the pancreas and kidney in which activated fibroblast-like cells or myofibroblasts are known to increase in number. In cultured hepatic stellate cells, Cygb/STAP expression was augmented by the stimulation with sera, platelet-derived growth factor-BB, and transforming growth factor-beta 1. Overexpression of Cygb/STAP in NIH 3T3 cells induced the cells to lessen migratory activities and increase the expression of collagen alpha1( I) mRNA. These results indicate that Cygb/STAP is a tissue globin uniquely localized in splanchnic fibroblastic cell lineage and may play a role in fibrotic organ disorder.