Identification and characterization of a fibroblast marker: FSP1.
Identification and characterization of a fibroblast marker: FSP1.
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DOI：
10.1083/jcb.130.2.393
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发表时间：
1995-07
期刊：
影响因子：
--
通讯作者：
Neilson EG
中科院分区：
文献类型：
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作者：
Strutz F;Okada H;Lo CW;Danoff T;Carone RL;Tomaszewski JE;Neilson EG
我们对小鼠成纤维细胞和同基因上皮细胞之间的转录本进行了差减和差异杂交比较，只观察到一些对成纤维细胞相对特异的新细胞内基因。一个这样的基因编码一种与钙离子结合的蛋白质，成纤维细胞特异性蛋白1（FSP 1）。驱动该基因的启动子/增强子区域在成纤维细胞中有活性，但在上皮细胞、系膜细胞或胚胎内胚层中无活性。在发育过程中，FSP 1首先通过原位杂交在第8.5天后作为原肠胚形成后事件检测到，并且与间充质来源的细胞或成纤维细胞表型相关。重组FSP 1蛋白的多克隆抗血清染色成纤维细胞的细胞质，但不是上皮细胞。在正常实质组织中，仅偶见细胞被特异性抗FSP 1抗体染色。然而，在持续性炎症导致的肾脏纤维化中，在胶原沉积的间质部位以及邻近炎症过程的肾小管上皮中可以识别出许多成纤维细胞。组织纤维化过程中的这种抗FSP 1染色模式表明，作为一种假设，在某些情况下，成纤维细胞根据需要从上皮的局部转化中产生。与FSP 1可能参与从上皮向成纤维细胞的转变的这一观点一致的是这样的实验，其中FSP 1cDNA在肾小管上皮中的体外过表达伴随着向间充质表型的转化，其特征在于更星状和伸长的成纤维细胞样外观、细胞角蛋白的减少和波形蛋白的新表达.类似地，浸没在I型胶原凝胶中的肾小管上皮细胞表现出向成纤维细胞表型的转化，其包括FSP 1和波形蛋白的从头表达。因此，FSP 1标记物的使用将进一步促进纤维发生的体内研究和成纤维细胞中细胞命运的映射。
We performed subtractive and differential hybridization for transcript comparison between murine fibroblasts and isogenic epithelium, and observed only a few novel intracellular genes which were relatively specific for fibroblasts. One such gene encodes a filament-associated, calcium-binding protein, fibroblast-specific protein 1 (FSP1). The promoter/enhancer region driving this gene is active in fibroblasts but not in epithelium, mesangial cells or embryonic endoderm. During development, FSP1 is first detected by in situ hybridization after day 8.5 as a postgastrulation event, and is associated with cells of mesenchymal origin or of fibroblastic phenotype. Polyclonal antiserum raised to recombinant FSP1 protein stained the cytoplasm of fibroblasts, but not epithelium. Only occasional cells stain with specific anti-FSP1 antibodies in normal parenchymal tissue. However, in kidneys fibrosing from persistent inflammation, many fibroblasts could be identified in interstitial sites of collagen deposition and also in tubular epithelium adjacent to the inflammatory process. This pattern of anti-FSP1 staining during tissue fibrosis suggests, as a hypothesis, that fibroblasts in some cases arise, as needed, from the local conversion of epithelium. Consistent with this notion that FSP1 may be involved in the transition from epithelium to fibroblasts are experiments in which the in vitro overexpression of FSP1 cDNA in tubular epithelium is accompanied by conversion to a mesenchymal phenotype, as characterized by a more stellate and elongated fibroblast- like appearance, a reduction in cytokeratin, and new expression of vimentin. Similarly, tubular epithelium submerged in type I collagen gels exhibited the conversion to a fibroblast phenotype which includes de novo expression of FSP1 and vimentin. Use of the FSP1 marker, therefore, should further facilitate both the in vivo studies of fibrogenesis and the mapping of cell fate among fibroblasts.