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      Transforming Growth Factor Beta Induces Urokinase Receptor Expression in Cultured Retinal Pigment Epithelial Cells

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          Abstract

          The effect of transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) and interferon-γ (IFN-γ) was studied on urokinase receptor (uPAR) expression of cultured human retinal pigment epithelial (RPE) cells. Human RPE cells were incubated with 1, 5 or 10 ng/ml of TGF-β<sub>1</sub> or with 10, 100 or 1,000 IU/ml of IFN-γ to measure total cellular uPAR protein and released uPAR by enzyme immunoassay. uPAR at cell surface was measured by flow cytometric analysis at 8, 12, 24 and 48 h. uPAR mRNA levels were assayed by Northern blotting at 2, 6, 12 and 24 h. The increase in uPAR gene expression in RPE cells exposed to TGF-β<sub>1</sub> paralleled enhanced uPAR level at the cell surface and in conditioned medium. TGF-β appeared to induce also membrane-bound uPA activity and the release of active plasminogen activator inhibitor-1, indicating that TGF-β has the potential to regulate plasminogen activation at the RPE cell surface. The increase in uPAR gene expression by IFN-γ did not seem to translate into the protein level. We conclude that TGF-β regulates the pericellular proteolysis in RPE cells by increasing uPAR expression.

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          Most cited references 2

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          Enhanced production and extracellular deposition of the endothelial- type plasminogen activator inhibitor in cultured human lung fibroblasts by transforming growth factor-beta

           M Laiho (1986)
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            Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor complexes

            Recent findings have elucidated the mechanism for clearance from the extracellular space of the two types of plasminogen activators, urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA), and their type-1 inhibitor (PAI-1). Activator/PAI-1 complexes and uncomplexed t-PA bind to the multi-ligand receptors alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR) and epithelial glycoprotein 330 (gp330). These receptors mediate endocytosis and degradation of u-PA/PAI-1 complex bound to the glycosyl phosphatidyl inositol-anchored urokinase receptor (u-PAR) on cell surfaces, and participate, in cooperation with other receptors, in hepatic clearance of activator/PAI-1 complexes and uncomplexed t-PA from blood plasma. The alpha 2MR- and gp330-mediated endocytosis of a ligand (u-PA/PAI-1 complex) initially bound to another receptor (u-PAR) is a novel kind of interaction between membrane receptors. Binding to alpha 2MR and gp330 is a novel kind of molecular recognition of serine proteinases and serpins.
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              Author and article information

              Journal
              ORE
              Ophthalmic Res
              10.1159/issn.0030-3747
              Ophthalmic Research
              S. Karger AG
              0030-3747
              1423-0259
              1999
              June 1999
              30 April 1999
              : 31
              : 3
              : 184-191
              Affiliations
              aDepartment of Virology, Haartman Institute, and bDepartment of Ophthalmology, University of Helsinki, Finland
              Article
              55531 Ophthalmic Res 1999;31:184–191
              10.1159/000055531
              10224501
              © 1999 S. Karger AG, Basel

              Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

              Page count
              Figures: 3, Tables: 1, References: 23, Pages: 8
              Categories
              Original Paper

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