Possible Interaction: Tissue Plasminogen Activator and Tretinoin

“When rats were pretreated with cholera toxin or retinoic acid to increase tPA synthesis, plasma levels of tPA were increased, whereas acute release of tPA, as induced by bradykinin, was increased to the same extent.”

“We show also that RA represses the transcriptional activity of a reporter gene containing a TPA responding AP1 binding site driving the HSV tk promoter.”

“We have shown that retinoic acid , applied either to the skin or administered in diet, inhibits skin tumor promotion by TPA.”

“ Retinoids inhibit both x-ray-induced transformation and its promotion by TPA ; these modifications (enhancement by TPA, inhibition by retinoids) are not reflected in sister chromatid exchanges, but are reflected in the level of membrane associated enzymes Na/K ATPase.”

“Surprisingly, low-dose RAs enhanced the activity of tissue-type plasminogen activator (tPA), and activated pro-matrix metalloproteinases (proMMP2 and proMMP9).”

“In the presence of the most potent retinoic acid metabolism inhibitor in endothelial cells, liarozole, at least 10-fold lower all-trans-retinoic acid concentrations were required than in the absence of the inhibitor to obtain the same induction of t-PA.”

“ Retinoic acid stimulates the expression of tissue-type plasminogen activator (t-PA) in vascular endothelial cells in vitro and enhances t-PA levels in plasma and tissues in vivo.”

“Conversely, with 2 microM retinoic acid , the mitogenic effect of PLG, IGFBP-2 proteolysis, and tissue-type PLG activator mRNAs were increased.”

“ RA and TPA added in combination synergistically enhanced expression of IL-8 mRNA, measured at 6 (2-fold) and 24 h (10-fold) posttreatment.”

“This latter effect was enhanced 2-fold by addition of RA and TPA together.”

“ Retinoic acid induces tissue-type plasminogen activator (t-PA) but not plasminogen activator inhibitor-1 (PAI-1) expression in cultured human umbilical vein endothelial cells (HUVEC).”

“Higher concentrations of t-RA (400 nmol/L) depressed tPA secretion by itself and also suppressed PMA-induced tPA production by 50%.”

“ Trans retinoic acid (t-RA) stimulated the production of tissue plasminogen activator (tPA) in HeLa-S3 and human umbilical vein endothelial cells (huvecs) in a dose-dependent manner with maximal release (four to five times control) at 40 nmol/L and 40 mumol/L, respectively.”