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Tissue distribution of factor VIII gene expression in vivo: a closer look

Academic Article
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Overview

authors

  • Hollestelle, M. J.
  • Thinnes, T.
  • Crain, K.
  • Stiko, A.
  • Kruijt, J. K.
  • van Berkel, T. J. C.
  • Loskutoff, David J.
  • van Mourik, J. A.

publication date

  • September 2001

journal

  • Thrombosis and Haemostasis  Journal

abstract

  • Previous studies have shown that factor VIII (FVIII) is expressed by multiple tissues. However, little is known about its cellular origin 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 (VWF). 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.

subject areas

  • Animals
  • Brain
  • Endothelium, Vascular
  • Factor VIII
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Immunochemistry
  • In Situ Hybridization
  • Kidney
  • Liver
  • Lung
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardium
  • Organ Specificity
  • Polymerase Chain Reaction
  • RNA, Messenger
  • Thromboplastin
  • Urokinase-Type Plasminogen Activator
  • von Willebrand Factor
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Research

keywords

  • biosynthesis
  • endothelial cell
  • factor VIII
  • von Willebrand factor
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Identity

International Standard Serial Number (ISSN)

  • 0340-6245

PubMed ID

  • 11583319
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Additional Document Info

start page

  • 855

end page

  • 861

volume

  • 86

issue

  • 3

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