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TJ Raife, EM Demetroulis and SR Lentz
Department of Pathology, University of Iowa College of Medicine, Iowa City,
USA.
Thrombomodulin is a cell-surface anticoagulant glycoprotein expressed by
vascular endothelial cells and epidermal keratinocytes. Thrombomodulin
expression in endothelial cells is regulated by retinoic acid and tumor
necrosis factor-alpha (TNF), agents that also modulate epidermal
differentiation. We examined thrombomodulin function and regulation of
thrombomodulin expression by all-trans retinoic acid (ATRA) and TNF in
human keratinocytes and endothelial cells. Untreated keratinocytes and
endothelial cells expressed thrombomodulin of comparable activity and
apparent thrombin affinity. Incubation of keratinocytes with 10 mumol/L
ATRA for 24 hours increased thrombomodulin activity 5.4 +/- 0.9-fold (mean
+/- SE), with equivalent increases observed in thrombomodulin protein (5.5
+/- 2.1-fold) and mRNA (4.2 +/- 1.2-fold). Incubation of keratinocytes with
1.0 nmol/L TNF markedly increased expression of keratinocyte
transglutaminase, but had no effect on thrombomodulin activity, protein, or
mRNA. In endothelial cells, ATRA produced a small increase in
thrombomodulin activity (1.9 +/- 0.1-fold), and incubation with TNF for 24
hours decreased thrombomodulin activity 83% +/- 7%. The activity profile of
keratinocyte thrombomodulin exhibited a distinct maximum near 1.0 mmol/L
Ca2+. These results demonstrate that keratinocyte thrombomodulin is
regulated by retinoids and Ca2+, but not by TNF, and that regulation of
thrombomodulin expression differs in keratinocytes and endothelial cells.
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