Open AccessEffect of retinoic acid on the synthesis of tissue‐type plasminogen activator and plasminogen activator inhibitor‐1 in human endothelial cells
Author(s) -
THOMPSON E. Anne,
NELLES Luc,
COLLEN Désiré
Publication year - 1991
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1991.tb16323.x
Subject(s) - retinoic acid , plasminogen activator , umbilical vein , plasminogen activator inhibitor 1 , microbiology and biotechnology , tissue plasminogen activator , chemistry , phorbol , t plasminogen activator , biology , medicine , endocrinology , protein kinase c , biochemistry , signal transduction , in vitro , gene
The synthesis of plasminogen activators and inhibitors in endothelial cells is highly regulated by hormones, drugs and growth factors. The present study evaluates the effect of retinoic acid on the synthesis of tissue‐type plasminogen activator (t‐PA) and of plasminogen activator inhibitor‐1 (PAI‐1) by cultured human umbilical vein endothelial cells (HUVEC). Retinoic acid produced a time‐ and concentration‐dependent increase in the secretion of t‐PA‐related antigen but not of PAI‐1 related antigen into the culture medium. A maximal sevenfold increase of t‐PA antigen after 24 h was observed with 10 μM and a half‐maximal increase with 0.1 μM retinoic acid. Retinoic acid induced a time‐dependent increase of the t‐PA mRNA, with a maximum at 8 h and returning to normal at 24 h. The protein kinase inhibitor H 7 decreased the t‐PA antigen induced by both retinoic acid and phorbol 12‐myristate 13‐acetate. These results suggest that treatment of HUVEC with retinoic acid increases t‐PA production by a pathway which, at some level, involves protein kinases. Thus, retinoic acid induces t‐PA synthesis in the absence of altered PAI‐1 synthesis, which may enhance the fibrinolytic potential of the endothelium.