Tissue distribution of factor VIII gene expression in vivo -: A closer look
Tissue distribution of factor VIII gene expression in vivo -: A closer look
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DOI：
10.1055/s-0037-1616143
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发表时间：
2001-09-01
影响因子：
6.7
通讯作者：
van Mourik, JA
中科院分区：
文献类型：
--
作者：
Hollestelle, MJ;Thinnes, T;van Mourik, JA
先前的研究表明，因子VIII（FVIII）由多种组织表达。然而，人们对其细胞起源知之甚少。或其在不同器官中的表达水平。在本研究中，我们研究了FVIII基因在不同组织中的表达定量的基础上。大多数组织，尤其是肝脏和肾脏，与其他止血蛋白（包括血管性血友病因子（WVF））的表达水平相比，FVIII mRNA表达水平较高。这是出乎意料的，因为FVIII是一种痕量蛋白质。原位杂交分析证实肝脏和肾脏富含FVIII mRNA。在肝脏中，在窦状隙内衬的细胞中检测到清晰的杂交信号。纯化肝细胞的FVIII mRNA分析证实了肝窦内皮细胞和枯否细胞表达FVIII mRNA。在肝细胞中也检测到低但显著水平的FVIII mRNA。在这些细胞中未检测到VWF mRNA。类似地，肝组织的免疫组织化学染色显示，FVIII蛋白主要与窦状隙细胞相关。VWF蛋白主要定位于大血管内皮。在肾脏中，FVIII合成定位于肾小球和肾小管上皮细胞。综上所述，这些结果表明，除肝细胞外，非实质细胞（例如窦状隙内皮细胞）也有助于FVIII合成。VWF的合成主要局限于肝外组织。
Previous studies have shown that factor VIII (FVIII) is expressed by multiple tissues. However, little is known about its cellular ori.-in or its level of expression in different organs. In the present study, we examined FVIII gene expression in different tissues on a quantitative basis. Most of the tissues, especially liver and kidney, expressed high levels of FVIII mRNA compared to their level of expression of other hemostatic proteins, including von Willebrand factor (WVF). This was unexpected since FVIII is a trace protein. In situ hybridization analysis confirmed that liver and kidney were rich in FVIII mRNA. In the liver, a clear hybridization signal was detected in cells lining the sinusoids. FVIII mRNA analysis of purified liver cells confirmed the expression of FVIII mRNA by sinusoidal endothelial cells and Kupffer cells. Low but significant levels of FVIII mRNA were also detected in the hepatocytes. VWF mRNA was not detectable in these cells. Similarly, immunohistochemical staining of liver tissue revealed that FVIII protein is primarily associated with sinusoidal cells. VWF protein was predominantly located in the endothelium of larger vessels. In the kidney, FVIII synthesis was localized to the glomeruli and to tubular epithelial cells. Taken together, these results suggest that besides hepatocytes, non-parenchymal cells (e.g. sinusoidal endothelial cells) contribute to FVIII synthesis. VWF synthesis is primarily confined to extra-hepatic tissues.