The aim of this study was to determine whether transforming growth factor-β1 (TGF-β1) induces the synthesis, release and gene expression of urokinase-type plasminogen activator (uPA) in hepatic stellate cells. In addition to stimulating collagen production, TGF-β1 induced the morphological and phenotypical changes characteristic of hepatic stellate cell activation. However, these changes accentuated in cells previously activated with acetaldehyde. TGF-β1 increased to 2-fold uPA activity in lysates from quiescent cells, and to 3.5-fold in activated cells, and induced uPA gene expression to the same extent in both activated and non-activated cells. TGF-β1 had a modest stimulatory action on the release of uPA into the conditioned medium, but reduced acetaldehyde-induced release, as demonstrated by Western blot analysis. In accord, whereas TGF-β1 produces no effect on uPA activity in the conditioned media from quiescent cells, it significantly reduces the stimulatory action of acetaldehyde. These results show that the activity and gene expression of uPA are regulated by both acetaldehyde and TGF-β1 and that the proteolytic activity in the extracellular space is reduced by the influence of TGF-β1. Further studies on the molecular mechanisms responsible for the regulation of the plasminogen system by TGF-β1 and other molecules in the presence of acetaldehyde will contribute to a better understanding of the processes involved in fibrogenesis.

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.