Regulation of ADAMTS13 expression in proliferating human umbilical vein endothelial cells.
ADAMTS13, the von Willebrand factor-cleaving protease, is constitutively produced by endothelial cells. The aim was to quantify ADAMTS13 production in proliferating and nonproliferating human umbilical vein endothelial cells (HUVECs) and to determine if such production was regulated. HUVECs were plated at 50,000 cells/cm(2) or 10,000 cells/cm(2), densities yielding confluence or subconfluence, respectively. Subconfluent HUVEC supernatants and cell lysates contained at least 2-fold more ADAMTS13 antigen than those of confluent HUVECs (p < 0.05). Immunohistochemistry supported this increase and indicated no dramatic shifts in subcellular localization of HUVEC ADAMTS13 by HUVEC proliferation. The activity of the ADAMTS13 produced by subconfluent HUVECs was increased about 2-fold also. HUVECs rapidly increased ADAMTS13 mRNA in response to subconfluent conditions. This change in regulation, in turn, leads to increased ADAMTS13 protein production and activity by these proliferating cells.
Kling
Stephen J
SJ
Division of Hematology, Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Judd
Cambria A
CA
Warner
Keith B
KB
Rodgers
George M
GM
D051722:ADAM Proteins / Q000235:genetics*; D000071120:ADAMTS13 Protein; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human