Possible Interaction: Tretinoin and Urokinase-Type Plasminogen Activator

“We investigated the molecular mechanism by which RA stimulates the expression of uPA , which lacks a canonical RA receptor (RAR)-responsive element, in bovine and human aortic endothelial cells.”

“ Trans retinoic acid (RA) also induced uPA mRNA and protein production in a dose‐dependent manner (10−6 to 10−9 M).”

“ All-trans retinoic acid lead to … in urokinase-type plasminogen activator (enzyme-linked immunosorbent assay) and urokinase-type plasminogen activator receptor cell surface expression (flow cytometry) after 24 h. At …-point, tissue-type plasminogen activator and plasminogen activator inhibitor-1 and -2 proteins were not or only slightly increased.”

“As tested in a chromogenic plasminogen activation assay, incubation with 10 microM all-trans retinoic acid caused a marked induction of cell-associated plasminogen activity after 24 h, and this induction was blocked by neutralizing anti-urokinase-type plasminogen activator antibodies , but not anti-tissue-type plasminogen activator antibodies.”

“On exposure of the cells to RA (10(-10)-10(-5) M) for 4 days, uPA secretion was increased 3.4-fold in the C8161 cell line and 1.6-fold in the Hs294T cell line using 10(-8) M RA.”

“RESULTS Both re inoids ca used a twofold to sevenfold increase in uro kinase-type plasminogen activator in the medium.”

“We have investigated the mechanism whereby all-trans retinoic acid (tRA) potentiates the 8-bromo-cAMP (8-BrcAMP)-dependent transcription of the urokinase plasminogen activator (uPA) gene in SC115 mouse mammary carcinoma cells.”

“Treatment of cultured HSCs with retinoic acid (1 μmol/L) increased uPA secretion 2.6‐fold but did not alter PAI‐1.”

“Upregulation of uPA synthesis by retinoic acid may have implications in matrix remodeling in sites of stellate cell activation in which high concentrations of retinoids may be achieved.”

“R4 effects were optimal at a concentration of M. In the presence of RA , proliferating cultures revealed increases in both uPA and tPA activity within 24 h of treatment which by 72 h was increased 2to 3-tbld fbr uPA activity and 5to lO-fbld fbr tPA activity (FIG.”

“Since we have previously shown that all-trans retinoic acid (RA) prevented the induction of uPA in mouse peritoneal macrophages, we have now assessed whether teratogenic doses of this agent could also interfere with uPA activity in mouse embryo in vitro and in vivo.”