High impact information on PLAU

• Pretreatment of BPAEC with anti-uPA antibody, and inhibitors of uPA (dansyl-GGACK) and plasmin (aprotinin) prevented approximately 60% of the fragment D-induced endothelial cell detachment [1].
• The effects of double mutations on k(a), k(lim), and k(app) were small with uPA and nonexistent with beta-trypsin [2].
• Treatment of cells with phosphatidylinositol-specific phospholipase C, which cleaves glycosylphosphatidylinositol-linked proteins from the cell surface, blocked the uPA-induced tyrosine phosphorylation of FAK, indicating the requirement of an intact uPAR on the cell surface [3].
• This may have important implications for the mechanism through which uPA influences cell migration and differentiation [3].
• The uPA-induced activation of MAPK was completely inhibited by genistein, but not by 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3, 4-d]pyrimidine, a specific inhibitor of Src family kinases [3].

Biological context of PLAU

• Insulin-like growth factor-I stimulated SERPINE2 secretion and uPA activity, and decreased secreted tPA activity and gene expression [4].
• Thus, this study demonstrates a novel role for the uPAR in endothelial cell signal transduction that involves the activation of FAK and MAPK, which are mediated by the receptor-binding domain of uPA [3].
• Nevertheless, a sustained ERK1/2 activation is not sufficient to trigger uPA upregulation and morphogenesis [5].
• During this time interval, the continuous presence of biologically active bFGF in the extracellular environment represented an absolute requirement for uPA mRNA translation [6].
• Accordingly, nuclear run-on experiments showed a 2-2.4-fold increase in the rate of uPA gene transcription during the first 4 h of treatment with the growth factor. bFGF did not affect uPA mRNA stability, as evaluated by chase experiments with the mRNA synthesis inhibitor actinomycin D [6].

Anatomical context of PLAU

• During ovarian follicle growth, there is expansion of the basal lamina and changes in the follicular extracellular matrix (ECM) that are mediated in part by proteolytic enzyme cascades regulated by tissue-type plasminogen activator (tPA) and urokinase plasminogen activator (uPA) [4].
• Vascular endothelial growth factor (VEGF) is a potent angiogenic factor and endothelial cell-specific mitogen that stimulates urokinase-type plasminogen activator (uPA) activity in vascular endothelial cells [7].
• However, cumulus cells play an essential role or roles in the production of uPA by oocytes, and EGF enhances the roles of cumulus cells [8].
• The specific immunofluorescence of cell surface uPA showed a patchy or strand-like distribution and was colocalized with vinculin strands indicating that uPA secreted from BCEs was mainly deposited at the cell surface of focal contacts [9].
• In the present study, expression and selected activities of urokinase-type plasminogen activator (uPA), matrix metalloproteinases (MMPs), their inhibitors (plasminogen activator inhibitor 1 (PAI-1) and tissue inhibitors of metalloproteinases (TIMPs)) were examined in bovine oviducts by RT--PCR, ribonuclease protection assay and activity assays [10].

Associations of PLAU with chemical compounds

• The serine proteinase plasmin is, together with tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), involved in the dissolution of blood clots in a fibrin-dependent manner [11].
• Heparin also increases the activity in mixtures of urokinase-type plasminogen activator (uPA) and plasminogen but has no effect on streptokinase or plasmin [12].
• Amiloride (uPA inhibitor) blocked the captopril-induced increase in EC survival, secondary sprouting, and invasion in Matrigel [13].
• RESULTS: All tested NSAIDs dose dependently inhibited the IL-1 induced mRNA expression of tPA, whereas only indomethacin and tiaprofenic acid were also able to reduce the expression of uPA [14].
• BCEs at a subconfluent density showed a higher intensity of specific immunofluorescence for uPA than when they were at a confluent density. tPA was observed over the dorsal surface of cultured BCEs and accentuated at their margins, suggesting that tPA was diffusely distributed on the luminal surface of BCEs in vivo [9].

Other interactions of PLAU

• Casein zymography revealed that the cells secreted predominantly tissue-type PA (tPA) with urokinase (uPA) being associated mainly with cell lysates, and Western blot demonstrated that the cells secreted SerpinE2 [15].
• Localization of tPA mRNA was primarily to the granulosal layer, whereas both uPA and uPAR mRNAs were detected in both the granulosal and thecal layers and adjacent ovarian stroma [16].
• Taken together, these findings demonstrate that VEGF-induced angiogenesis is accompanied by increased uPAR expression and uPA activity on the endothelial cell surface [7].
• Both drugs inhibited the IL-1-induced mRNA expression of tPA, whereas expression of uPA was only mildly reduced by PSGAG, which also induced PAI-1 above IL-1 stimulated levels [17].

Analytical, diagnostic and therapeutic context of PLAU

• Changes in the expression of urokinase-type PA (uPA), uPA receptor, and PAI-1 mRNA in BAEC after treatment with Rb2 were analyzed by Northern blot [18].
• The levels of MMPs, TIMPs, uPA, tPA, and PAI-1 gene expression were estimated by determining the mRNA levels using real-time PCR, and the protein levels were determined using ELISA [19].
• Quantitative densitometry showed a six- to eightfold decrease in coculture uPA during capillary-like structure formation [20].
• A three- to four-fold increase in the steady-state levels of uPA mRNA was observed after 6 h of incubation of the cell cultures with bFGF [6].

References