Expression of hepatocyte growth factor activator inhibitor type 1 in endothelial cells

Hum Cell. 2006 Aug;19(3):91-7. doi: 10.1111/j.1749-0774.2006.00015.x.

Abstract

Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is an integral membrane Kunitz-type serine proteinase inhibitor initially identified as a potent inhibitor of hepatocyte growth factor activator (HGFA). HGFA is a serum proteinase that is critically involved in the activation of hepatocyte growth factor/scatter factor (HGF/SF) in injured tissue. Previous studies have shown that HAI-1 is expressed on the basolateral surface of various epithelial cells. In this study, we analyzed the expression of HAI-1 in human endothelial cells. Immunohistochemically, HAI-1 protein was observed in the endothelial cells of capillaries, venules and lymph vessels. On the other hand, arterial endothelial cells were poorly stained for HAI-1. Mesothelial cells on the serous surface were also positively immunostained. The endothelial expression of HAI-1 was also examined in cultured human endothelial cells of various origins, such as umbilical vein, microvessels and aorta. Notably, in accordance with the results of immunohistochemistry, HAI-1 mRNA and protein levels were high in the endothelial cells derived from umbilical vein and were hardly detectable in those derived from aorta. A low but distinct level of HAI-1 expression was also observed in endothelial cells from microvessels. As these HAI-1-positive endothelial cells also expressed MET tyrosine kinase, the specific receptor of HGF/SF, it is conceivable that HAI-1 might have an important regulatory role in the HGF/SF-MET signaling axis of endothelial cells, which could be involved in the process of angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Endothelial Cells / enzymology*
  • Hepatocyte Growth Factor / metabolism
  • Hepatocyte Growth Factor / physiology
  • Humans
  • Immunohistochemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Neovascularization, Pathologic / genetics
  • Proteinase Inhibitory Proteins, Secretory
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-met
  • RNA, Messenger / metabolism
  • Receptors, Growth Factor / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction

Substances

  • Membrane Glycoproteins
  • Proteinase Inhibitory Proteins, Secretory
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Growth Factor
  • SPINT1 protein, human
  • Hepatocyte Growth Factor
  • MET protein, human
  • Proto-Oncogene Proteins c-met