Urokinase Induces Expression of Its Own Receptor in Beas2B Lung Epithelial Cells

Abstract

Interaction between the urokinase-type plasminogen activator (uPA) and its receptor (uPAR) localizes cellular proteolysis and promotes cellular proliferation and migration. The interaction between uPA and uPAR at the surface of epithelial cells thereby contributes to the pathogenesis of lung inflammation and neoplasia. In this study, we sought to determine if uPA itself alters uPAR expression by lung epithelial cells. uPA enhanced uPAR expression as well as 125 I-uPA binding in Beas2B lung epithelial cells in a time-and concentration-dependent manner. The uPA-mediated induction of uPAR is not accomplished through its receptor and requires enzymatic activity. The low molecular weight fragment of uPA, lacking the receptor binding domain, was as potent as intact two-chain uPA in inducing expression of uPAR at the cell surface. Plasmin, the end product of plasminogen activation, did not alter uPA-mediated uPAR expression. Induction of uPAR by uPA represents a novel pathway by which epithelial cells can regulate uPAR-dependent cellular responses that may contribute to stromal remodeling in lung injury or neoplasia.

Post-Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor Expression in Lipopolysaccharide-induced Acute Lung Injury

“…These cells were maintained in LHC-9 medium containing insulin, hydrocortisone, epidermal growth factor, transferrin, T3, retinoic acid, epinephrine, gentamycin, bovine pituitary extracts, and 1% antibiotics, as previously described (28). Cells were grown to subconfluence, and were serum starved overnight in RPMI 1,640 media.…”

Regulation of Plasminogen Activator Inhibitor-1 Expression by Tumor Suppressor Protein p53

“…Effect of p53 Binding PAI-1 mRNA 3Ј-UTR Sequence on PAI-1 Expression-Chimeric mRNAs were created using methods we reported previously (21,22). H1299 cells expressing vector cDNA or p53 cDNA were transfected with chimeric ␤-globin/ PAI-1 cDNA containing the 70-nt p53 protein-binding sequence of the PAI-1 mRNA 3Ј-UTR or control non-p53 binding CDR sequences as described above for 48 h to competitively inhibit p53 binding to endogenous PAI-1 mRNA.…”

“…H1299 cells were transfected with vector cDNA or vector containing p53 cDNA, and stable cell lines were created as described earlier (22). The cells were treated with PBS or uPA, and the effect of p53 expression on basal and uPA-mediated p53, PAI-1 protein and mRNA levels was analyzed by Western or Northern blotting, respectively, as described above.…”

Stable expression of antisense urokinase mRNA inhibits the proliferation and invasion of human hepatocellular carcinoma cells

“…26,27 Our results are in line with what is known about the ability of u -PA to up -regulate the expression of its cellular receptor at a transcriptional level, by increasing the activity of the transcriptional factor Sp1, and also at a posttranscriptional level, by promoting u -PAR mRNA stability. 28,29 The drop in u -PA would, therefore, down -regulate the expression of its receptor as detected in our experimental system. The expression of other genes, which could be related to the u -PA phenotype, such as PAI -1, t -PA, FN, and c -met (HGF receptor ), was also tested.…”