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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor-beta 1 (TGF-beta 1) induces a decrease in plasminogen activator (PA) expression in confluent cultures of bovine aortic endothelial (BAE) cells. We describe an assay using the suppression of PA expression in confluent BAE cells by TGF-beta 1 which detects concentrations of the growth factor ranging from 5 to 200 pg/ml and has an ED50 of 15-20 pg/ml. The assay can be performed in 96-well plates and requires a minimum of 35 ul of solution per sample, thereby limiting the amount of reagents required and allowing many samples to be tested in a single assay. Here we demonstrate that the effect of TGF-beta 1 on PA expression in BAE cells depends on the length of time the cells are exposed to the growth factor and the density at which the cells are plated. In cells plated at a high density (3.5 x 10(5) cells/cm2), both 4 h and 24 h exposures to TGF-beta 1 suppress PA expression. However, with cells plated sparsely (3.5 x 10(4) cells/cm2), a 4 h exposure to TGF-beta 1 increases PA expression 2-fold, whereas a 24 h exposure results in an 85% inhibition of basal PA expression. The paradoxical stimulation of PA expression in cells at a sparse density upon 4 h exposure to TGF-beta 1 occurs in a dose-dependent manner with an ED50 of 15-20 pg/ml. This bifunctional response of PA production in cells exposed to TGF-beta 1 may have implications with regard to the role of TGF-beta 1 in angiogenesis.
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PMID:Cell density dependent effects of TGF-beta demonstrated by a plasminogen activator-based assay for TGF-beta. 161 22

Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in the positive regulation of angiogenesis in vivo, whereas it inhibits the proliferation of endothelial cells in vitro. To reconcile these apparently contradictory effects, we have investigated the effect of TGF-beta 1 on bovine aortic endothelial cells that exhibit spontaneous angiogenesis in vitro. We show that concentrations of TGF-beta 1 which stimulate proliferation of cells that form endothelial cords and/or tubes inhibit proliferation of the same cells grown at subconfluent densities. An increase in cell number of 35% over control cultures was achieved with 0.5 ng TGF-beta 1/ml. The proliferative effect was blocked by antibodies against TGF-beta. Immunological detection of BrdU-labeled nuclei revealed an increase greater than 220% in cells treated with TGF-beta 1. Moreover, a population of cells within the cords appeared to be a selective target for this cytokine. The stimulatory effect was not restricted to bovine aortic endothelial cells, as similar results were obtained with endothelial cells derived from rat microvessels. Significant levels of active TGF-beta 1 were detected in cultures containing cords/tubes, whereas only latent TGF-beta 1 was detected in subconfluent cultures. We show further that endothelial cells exhibiting angiogenesis in vitro secrete plasminogen activator, an enzyme that regulates activation of TGF-beta. The major increases in mRNA transcripts for extracellular matrix proteins that are typically associated with TGF-beta 1 were not seen in cells exhibiting angiogenesis in vitro. Since the formation of tubular networks requires both invasion and proliferation, we propose that TGF-beta 1 is a major morphoregulatory factor in angiogenesis that specifically controls endothelial cell proliferation and extracellular matrix turnover.
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PMID:Endothelial cells exhibiting angiogenesis in vitro proliferate in response to TGF-beta 1. 769 28