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      α-Thrombin Induces Transforming Growth Factor-β 1 mRNA and Protein in Cultured Vascular Smooth Muscle Cells via a Proteolytically Activated Receptor

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          Abstract

          The potent growth factors and chemoattractants α-thrombin and transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) have both been identified at sites of arterial injury, however the interaction between these two factors has not been defined. By Northern hybridization analyses, accumulation of both a 1.9- and a 2.4-kb transcript of TGF-β<sub>1</sub> were detected and occurred in a time- and dose-dependent fashion following α-thrombin stimulation of cultured vascular smooth muscle cells (VSMC). This induction of TGF-β<sub>1</sub> mRNA required the proteolytic activity of thrombin and was mimicked by a thrombin-receptor-(TR)-activating peptide or TRAP (SFFLRNP). Increases in α-thrombin-induced TGF-β<sub>1</sub> message expression were insensitive to cycloheximide, but sensitive to actinomycin D. Furthermore, the induction of TGF-β<sub>1</sub>. mRNA expression correlated with the production of latent TGF-β<sub>1</sub> protein in α-thrombin-conditioned media. In summary, α-thrombin stimulation of VSMC induces transcriptional activation of the TGF-β<sub>1</sub> gene through proteolytic activation of the cloned seven-transmembrane TR resulting in the formation of latent TGF-β<sub>1</sub> protein. These results demonstrate a potential mechanism whereby α-thrombin may modulate the vascular response to injury through TGF-β<sub>1</sub>-dependent mechanisms.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1997
          1997
          24 September 2008
          : 34
          : 1
          : 41-48
          Affiliations
          Departments of aMedicine and bMolecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Va., USA
          Article
          159200 J Vasc Res 1997;34:41–48
          10.1159/000159200
          9075824
          © 1997 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
          Pages: 8
          Categories
          Research Paper

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