Coupled stimulation of cell migration and seprase expression in human endothelial cells by sphingosine 1 -phosphate

摘要

Sphingosine 1-phosphate (Sph-1-P), a bioactive lysophospholipid present in the plasma, is released from activated platelets. Our previous study demonstrated that Sph-1-P promoted the spreading on and migration of human umbilical vein endothelial cells (HUVEC) through the extracellular matrix (ECM), suggesting a possible induction of cell surface proteases. Here we provide the evidence that seprase, a type II transmembrane serine protease (TTSP), can be induced in endothelial cells activated by Sph-1-P. We show by immunoblot analysis using anti-seprase monoclonal antibodies (mAbs) that Sph-1-P enhanced expression of seprase in a time- and dose-dependent manner in HUVEC. The Sph-1-P inducible seprase could be blocked by pertussis toxin and by C3 transferase, which inactivate Gi-type heterotrimetric G proteins and Rho, respectively. These results show that Sph-1-P can regulate migration of endothelial cells by inducing seprase expression through a Gi-typed protein and the Rho protein.