Monkey Hepatocytes Efficiently Express Tissue Factor Pathway Inhibitor (TFPI), in Contrast with Human and Rat Hepatocytes

Abstract

It has been reported that tissue factor pathway inhibitor (TFPI), a Kunitz-type protease inhibitor that regulates the extrinsic blood coagulation pathway, is not expressed in human, bovine, rabbit, or rat liver. Here, we found that TFPI is efficiently expressed in Macaque monkey liver. Monkey hepatocytes were identified as the expression cells by Northern blot analysis. The hepatocytes were stained with anti-human TFPI antibody, as were endothelial cells of the small vessels. We isolated and sequenced the 5'-flanking 1.4 kb regions of monkey and human TFPI genes, and found them to show 92.6% identity in their nucleotide sequences. We measured their transcriptional activities using a luciferase reporter gene and showed that the activity of the monkey TFPI gene is higher than that of the human gene in monkey primary hepatocytes. Although the binding motif of hepatocyte nuclear factor-1 is present only in the monkey gene, the site does not seem to be involved in the transcriptional activity. Mutagenetic analyses revealed that the region from -138 to +28 in the monkey gene is important for the expression of TFPI in hepatocytes. The present study indicates that the expression of the monkey TFPI gene is regulated by different mechanisms from the human TFPI gene.